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Dystonia - complex v0.235 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Dystonia - complex v0.234 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.234 PAH Natalie Lim gene: PAH was added
gene: PAH was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAH were set to PMID: 25614310, PMID: 15390012, PMID: 30369906
Phenotypes for gene: PAH were set to Phenylketonuria MIM#261600
Review for gene: PAH was set to GREEN
Added comment: Reports of parkinsonism and dystonia have been documented as delayed manifestations amongst PKU patients although rare.
Sources: Expert Review
Dystonia - complex v0.234 NAA15 Shekeeb Mohammad gene: NAA15 was added
gene: NAA15 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: NAA15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NAA15 were set to 38380600
Phenotypes for gene: NAA15 were set to dystonia; neurodevelopmental delay
Penetrance for gene: NAA15 were set to unknown
Review for gene: NAA15 was set to GREEN
Added comment: previous 3 cases in literature referenced in 38380600
Sources: Literature
Dystonia - complex v0.234 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Dystonia - complex v0.234 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Dystonia - complex v0.233 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Dystonia - complex v0.233 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Dystonia - complex v0.232 ACBD6 Elena Savva Marked gene: ACBD6 as ready
Dystonia - complex v0.232 ACBD6 Elena Savva Gene: acbd6 has been removed from the panel.
Dystonia - complex v0.232 ACBD6 Lucy Spencer gene: ACBD6 was added
gene: ACBD6 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 37951597
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related
Review for gene: ACBD6 was set to GREEN
Added comment: PMID: 37951597
45 individuals from 28 families with a neurodevelopmental syndrome with complex and progressive movement disorder phenotype. 18 PTCs and splice, 1 missense 1 in frame insertion.

Phenotypes: weight was >50th percentile in 20/34 patients, all mod-severe GDD, facial dysmorphism in 38/40, mild cerebellar ataxia 35/41, limb spasticity/hypertonia 31/41, gait abnormalities in 33/35, dystonia in 30/31.
Sources: Literature
Dystonia - complex v0.232 MAPT Bryony Thompson edited their review of gene: MAPT: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Dystonia - complex v0.232 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Dystonia - complex v0.231 ATP2B2 Andrew Fennell gene: ATP2B2 was added
gene: ATP2B2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B2 were set to PMID: 37675773
Phenotypes for gene: ATP2B2 were set to Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related
Mode of pathogenicity for gene: ATP2B2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ATP2B2 was set to GREEN
Added comment: 7 unrelated individuals reported with a variable phenotype including dystonia, ataxia, intellectual disability, behavioural symptoms, and seizures.

All patients have either missense variants or frameshift variants in the penultimate exon not expected to lead to NMD. This is in contrast to patients with isolated deafness previously reported to have nonsense, frameshift, or splice-site variants outside of this region.
Sources: Literature
Dystonia - complex v0.231 SHQ1 Zornitza Stark Publications for gene: SHQ1 were set to 34542157; 29178645
Dystonia - complex v0.230 SHQ1 Zornitza Stark Classified gene: SHQ1 as Green List (high evidence)
Dystonia - complex v0.230 SHQ1 Zornitza Stark Gene: shq1 has been classified as Green List (High Evidence).
Dystonia - complex v0.229 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Added comment: Two more individuals with dystonia reported.; Changed rating: GREEN; Changed publications: 34542157, 29178645, 36847845, 37475611
Dystonia - complex v0.229 EIF4A2 Zornitza Stark Phenotypes for gene: EIF4A2 were changed from Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, MIM# 620455
Dystonia - complex v0.228 EIF4A2 Zornitza Stark Marked gene: EIF4A2 as ready
Dystonia - complex v0.228 EIF4A2 Zornitza Stark Gene: eif4a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.228 EIF4A2 Zornitza Stark Phenotypes for gene: EIF4A2 were changed from DYSTONIA; TREMOR to Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related
Dystonia - complex v0.227 EIF4A2 Zornitza Stark Classified gene: EIF4A2 as Green List (high evidence)
Dystonia - complex v0.227 EIF4A2 Zornitza Stark Gene: eif4a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.226 EIF4A2 Zornitza Stark edited their review of gene: EIF4A2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.226 EIF4A2 Zornitza Stark reviewed gene: EIF4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - complex v0.226 EIF4A2 Shekeeb Mohammad gene: EIF4A2 was added
gene: EIF4A2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: EIF4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF4A2 were set to 37485550
Phenotypes for gene: EIF4A2 were set to DYSTONIA; TREMOR
Penetrance for gene: EIF4A2 were set to unknown
Review for gene: EIF4A2 was set to GREEN
Added comment: Sources: Literature
Dystonia - complex v0.226 TSPOAP1 Zornitza Stark Marked gene: TSPOAP1 as ready
Dystonia - complex v0.226 TSPOAP1 Zornitza Stark Gene: tspoap1 has been classified as Green List (High Evidence).
Dystonia - complex v0.226 TSPOAP1 Zornitza Stark Phenotypes for gene: TSPOAP1 were changed from dystonia; intellectual disability; cerebellar atrophy to Dystonia 22, MIM# 620453
Dystonia - complex v0.225 TSPOAP1 Zornitza Stark Classified gene: TSPOAP1 as Green List (high evidence)
Dystonia - complex v0.225 TSPOAP1 Zornitza Stark Gene: tspoap1 has been classified as Green List (High Evidence).
Dystonia - complex v0.224 TSPOAP1 Zornitza Stark reviewed gene: TSPOAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 22, MIM# 620453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.224 NUP54 Zornitza Stark Phenotypes for gene: NUP54 were changed from Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Dystonia 37, early-onset, with striatal lesions, MIM# 620427; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Dystonia - complex v0.223 SLC30A9 Zornitza Stark Marked gene: SLC30A9 as ready
Dystonia - complex v0.223 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Dystonia - complex v0.223 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Dystonia - complex v0.223 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Dystonia - complex v0.222 SLC30A9 Lucy Spencer gene: SLC30A9 was added
gene: SLC30A9 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A9 were set to 37041080
Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome (MIM#617595)
Review for gene: SLC30A9 was set to GREEN
Added comment: PMID:37041080 - 2 families previously reported and this paper describes 4 more with biallelic SLC30A9 variants. Original 2 families: 6 affected members all hom for Ala350del, and 1 affected member chet for 2 frameshifts. 4 families from this paper: 2 families have the same homozygous missense (Gly418Val), family 3 has 4 affected sibs hom for Ala350del, family 4 1 affected chet for a frameshift and a synonymous. So 2 fams homs for Ala350del and 2 fams hom for Gly418Val.
All have Brik-Landau-Perez syndrome: all with ID, movement disorder and dystonia, and many with oculomotor apraxia, renal abnormalitie, ptosis, some had hearing impairment.
Sources: Literature
Dystonia - complex v0.222 TRPM3 Zornitza Stark Marked gene: TRPM3 as ready
Dystonia - complex v0.222 TRPM3 Zornitza Stark Gene: trpm3 has been classified as Green List (High Evidence).
Dystonia - complex v0.222 TRPM3 Zornitza Stark Phenotypes for gene: TRPM3 were changed from Intellectual disability; epilepsy; chorea; athetosis; hypotonia; dysmorphic features to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, MIM# 620224
Dystonia - complex v0.221 TRPM3 Zornitza Stark Classified gene: TRPM3 as Green List (high evidence)
Dystonia - complex v0.221 TRPM3 Zornitza Stark Gene: trpm3 has been classified as Green List (High Evidence).
Dystonia - complex v0.220 TRPM3 Zornitza Stark reviewed gene: TRPM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, MIM# 620224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.220 TRPM3 Shekeeb Mohammad gene: TRPM3 was added
gene: TRPM3 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM3 were set to 31278393; 35146895
Phenotypes for gene: TRPM3 were set to Intellectual disability; epilepsy; chorea; athetosis; hypotonia; dysmorphic features
Penetrance for gene: TRPM3 were set to Complete
Review for gene: TRPM3 was set to GREEN
gene: TRPM3 was marked as current diagnostic
Added comment: Sources: Literature
Dystonia - complex v0.220 NUP54 Zornitza Stark Marked gene: NUP54 as ready
Dystonia - complex v0.220 NUP54 Zornitza Stark Gene: nup54 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.220 NUP54 Zornitza Stark Classified gene: NUP54 as Amber List (moderate evidence)
Dystonia - complex v0.220 NUP54 Zornitza Stark Gene: nup54 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.219 NUP54 Zornitza Stark gene: NUP54 was added
gene: NUP54 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: NUP54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP54 were set to 36333996
Phenotypes for gene: NUP54 were set to Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Review for gene: NUP54 was set to AMBER
Added comment: From PMID: 36333996.; Harrer, P. et al. (2022) Ann Neurol. doi: 10.1002/ana.26544.

Three patients from unrelated families with dystonia and/or Leigh(-like) syndromes, with biallelic variants in NUP54, in the C-terminal protein region that interacts with NUP62. Onset was between 12 months and 5 years. All had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

Patient / Family A (consanguineous) was homozygous for c.1073T>G p.(Ile358Ser).

Patient / Family B was compound heterozygous for c.1073T>G p.(Ile358Ser) and c.1126A>G p.(Lys376Glu).

Patient / Family C was compound heterozygosity for c.1410_1412del p.(Gln471del) and two missense variants c.1414G>A, p.(Glu472Lys); c.1420C>T, p.(Leu474Phe)

The phenotypes were similar to those of NUP62 including early-onset dystonia with dysphagic choreoathetosis, and T2-hyperintense lesions in striatum.

Brain MRIs showed T2/FLAIR hyperintensities in the dorsal putamina.

Western blots showing reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts.
Sources: Literature
Dystonia - complex v0.218 Zornitza Stark HPO terms changed from to Dystonia, HP:0001332
List of related panels changed from to Dystonia; HP:0001332
Dystonia - complex v0.217 GAMT Zornitza Stark Tag treatable tag was added to gene: GAMT.
Dystonia - complex v0.217 DDC Zornitza Stark Tag treatable tag was added to gene: DDC.
Tag clinical trial tag was added to gene: DDC.
Dystonia - complex v0.217 COQ8A Zornitza Stark Tag treatable tag was added to gene: COQ8A.
Dystonia - complex v0.217 GALT Zornitza Stark Tag treatable tag was added to gene: GALT.
Dystonia - complex v0.217 PCCB Zornitza Stark Tag treatable tag was added to gene: PCCB.
Dystonia - complex v0.217 PCCA Zornitza Stark Tag treatable tag was added to gene: PCCA.
Dystonia - complex v0.217 QDPR Zornitza Stark Tag treatable tag was added to gene: QDPR.
Dystonia - complex v0.217 PTS Zornitza Stark Tag treatable tag was added to gene: PTS.
Dystonia - complex v0.217 GCDH Zornitza Stark Tag treatable tag was added to gene: GCDH.
Dystonia - complex v0.217 AFG3L2 Zornitza Stark Publications for gene: AFG3L2 were set to 22964162; 16541453; 32219868
Dystonia - complex v0.216 AFG3L2 Zornitza Stark Classified gene: AFG3L2 as Amber List (moderate evidence)
Dystonia - complex v0.216 AFG3L2 Zornitza Stark Gene: afg3l2 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.215 ARSA Zornitza Stark Tag treatable tag was added to gene: ARSA.
Tag clinical trial tag was added to gene: ARSA.
Dystonia - complex v0.215 AFG3L2 Shekeeb Mohammad reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36110148; Phenotypes: dystonia, parkinsonism, intellectual disability, optic hypoplasia, dementia, cognitive decline; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Dystonia - complex v0.215 SHQ1 Zornitza Stark Phenotypes for gene: SHQ1 were changed from Dystonia; Neurodegeneration to Dystonia 35, childhood-onset , MIM# 619921; Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Dystonia - complex v0.214 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Changed phenotypes: Dystonia 35, childhood-onset , MIM# 619921, Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Dystonia - complex v0.214 NR4A2 Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual Disability; Dystonia and Early-onset Parkinson to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Dystonia - complex v0.213 ZNF526 Zornitza Stark Phenotypes for gene: ZNF526 were changed from Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia to Dentici-Novelli neurodevelopmental syndrome, MIM# 619877
Dystonia - complex v0.212 ZNF526 Zornitza Stark edited their review of gene: ZNF526: Changed phenotypes: Dentici-Novelli neurodevelopmental syndrome, MIM# 619877
Dystonia - complex v0.212 FBXO28 Zornitza Stark Marked gene: FBXO28 as ready
Dystonia - complex v0.212 FBXO28 Zornitza Stark Gene: fbxo28 has been classified as Green List (High Evidence).
Dystonia - complex v0.212 FBXO28 Zornitza Stark Phenotypes for gene: FBXO28 were changed from infantile spasms; developmental epileptic encephalopathy; microcephaly; hypotonia; dystonia; intellectual disability; progressive myoclonic epilepsy to Developmental and epileptic encephalopathy 100, MIM# 619777
Dystonia - complex v0.211 FBXO28 Zornitza Stark Classified gene: FBXO28 as Green List (high evidence)
Dystonia - complex v0.211 FBXO28 Zornitza Stark Gene: fbxo28 has been classified as Green List (High Evidence).
Dystonia - complex v0.210 FBXO28 Zornitza Stark reviewed gene: FBXO28: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 100, MIM# 619777; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.210 TNPO2 Zornitza Stark Marked gene: TNPO2 as ready
Dystonia - complex v0.210 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Dystonia - complex v0.210 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from global developmental delay; dysmorphic features; ophthalmologic abnormalities; intellectual disability; fever induced seizures; epilepsy, dystonia; cerebellar dysplasia; cerebllar dysplasia; microcephaly to Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556
Dystonia - complex v0.209 TNPO2 Zornitza Stark Classified gene: TNPO2 as Green List (high evidence)
Dystonia - complex v0.209 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Dystonia - complex v0.208 FBXO28 Shekeeb Mohammad gene: FBXO28 was added
gene: FBXO28 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: FBXO28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXO28 were set to 33280099
Phenotypes for gene: FBXO28 were set to infantile spasms; developmental epileptic encephalopathy; microcephaly; hypotonia; dystonia; intellectual disability; progressive myoclonic epilepsy
Penetrance for gene: FBXO28 were set to unknown
Review for gene: FBXO28 was set to GREEN
gene: FBXO28 was marked as current diagnostic
Added comment: Sources: Literature
Dystonia - complex v0.208 TNPO2 Shekeeb Mohammad edited their review of gene: TNPO2: Set current diagnostic: yes
Dystonia - complex v0.208 TNPO2 Shekeeb Mohammad gene: TNPO2 was added
gene: TNPO2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNPO2 were set to 34314705
Phenotypes for gene: TNPO2 were set to global developmental delay; dysmorphic features; ophthalmologic abnormalities; intellectual disability; fever induced seizures; epilepsy, dystonia; cerebellar dysplasia; cerebllar dysplasia; microcephaly
Penetrance for gene: TNPO2 were set to unknown
Review for gene: TNPO2 was set to GREEN
Added comment: The movement disorder noted is a complex dystonia, with hyperkinetic components and some patients have episodic exacerbations
Sources: Literature
Dystonia - complex v0.208 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Dystonia - complex v0.208 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Dystonia - complex v0.208 WARS2 Zornitza Stark Classified gene: WARS2 as Green List (high evidence)
Dystonia - complex v0.208 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Dystonia - complex v0.207 WARS2 Zornitza Stark gene: WARS2 was added
gene: WARS2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS2 were set to 29120065; 31970218; 34890876; 28236339; 28650581; 28905505; 30920170
Phenotypes for gene: WARS2 were set to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710
Review for gene: WARS2 was set to GREEN
Added comment: Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. 8 individuals from 4 families reported.

NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding. 12 individuals from 8 unrelated families reported.

It is unclear whether these are two distinct disorders or whether they represent a spectrum of severity for a single condition.
Sources: Literature
Dystonia - complex v0.206 GAMT Zornitza Stark Publications for gene: GAMT were set to 19027335
Dystonia - complex v0.205 GAMT Zornitza Stark Classified gene: GAMT as Green List (high evidence)
Dystonia - complex v0.205 GAMT Zornitza Stark Gene: gamt has been classified as Green List (High Evidence).
Dystonia - complex v0.204 GAMT Zornitza Stark reviewed gene: GAMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 19027335, 33996490, 12557293, 19288536, 16855203; Phenotypes: Cerebral creatine deficiency syndrome 2 MIM#612736; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.204 AFG3L2 Zornitza Stark Phenotypes for gene: AFG3L2 were changed from Spastic ataxia 5, autosomal recessive MIM#614487 to Spastic ataxia 5, autosomal recessive MIM#614487; Early-onset dystonia
Dystonia - complex v0.203 AFG3L2 Zornitza Stark Publications for gene: AFG3L2 were set to 22964162; 16541453
Dystonia - complex v0.202 AFG3L2 Zornitza Stark Mode of inheritance for gene: AFG3L2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - complex v0.201 AFG3L2 Zornitza Stark reviewed gene: AFG3L2: Rating: RED; Mode of pathogenicity: None; Publications: 32219868; Phenotypes: Early-onset dystonia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - complex v0.201 ATP5G3 Zornitza Stark Marked gene: ATP5G3 as ready
Dystonia - complex v0.201 ATP5G3 Zornitza Stark Gene: atp5g3 has been classified as Green List (High Evidence).
Dystonia - complex v0.201 ATP5G3 Zornitza Stark Classified gene: ATP5G3 as Green List (high evidence)
Dystonia - complex v0.201 ATP5G3 Zornitza Stark Gene: atp5g3 has been classified as Green List (High Evidence).
Dystonia - complex v0.200 ATP5G3 Zornitza Stark gene: ATP5G3 was added
gene: ATP5G3 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: ATP5G3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5G3 were set to 34636445; 34954817
Phenotypes for gene: ATP5G3 were set to Dystonia, early-onset, and/or spastic paraplegia, MIM# 619681
Review for gene: ATP5G3 was set to GREEN
Added comment: Note that HGNC approved gene name is ATP5MC3.

PMID: 34636445 reports a missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia. The variant was identified via exome sequencing of the proband and a distant cousin, focussing on variants within the previously determined linkage region. The identical missense variant was also identified in a patient with childhood onset dystonic syndrome and was shown to be de novo. Functional studies of fibroblast cell lines from affected father (HSP) and proband of large family demonstrated decreased complex V function. A drosophila model containing the missense variant had reduced mobility and reduced complex V activity.

PMID: 34954817 reports de novo monoallelic missense variants in three individuals, however one of these individuals was reported in above paper. The other two patients were: (1) a-15-year-old girl with milestone delay, pyramidal signs, and generalized dystonia with prominent upper-body involvement, and (2) a 6-year-old boy with delayed psychomotor development, lower-extremity spasticity, and elevated blood lactate levels
Sources: Literature
Dystonia - complex v0.199 GNB1 Zornitza Stark Mode of inheritance for gene: GNB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.198 SPATA5L1 Zornitza Stark Phenotypes for gene: SPATA5L1 were changed from Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss to Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616
Dystonia - complex v0.197 SPATA5L1 Zornitza Stark reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.197 SPATA5L1 Zornitza Stark Marked gene: SPATA5L1 as ready
Dystonia - complex v0.197 SPATA5L1 Zornitza Stark Gene: spata5l1 has been classified as Green List (High Evidence).
Dystonia - complex v0.197 SPATA5L1 Zornitza Stark Classified gene: SPATA5L1 as Green List (high evidence)
Dystonia - complex v0.197 SPATA5L1 Zornitza Stark Gene: spata5l1 has been classified as Green List (High Evidence).
Dystonia - complex v0.196 SPATA5L1 Paul De Fazio gene: SPATA5L1 was added
gene: SPATA5L1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss
Review for gene: SPATA5L1 was set to GREEN
gene: SPATA5L1 was marked as current diagnostic
Added comment: 47 individuals from 26 unrelated families from various ethnicities with biallelic variants reported. Phenotypes include ID, hearing impairment, movement disorder, abnormal MRI, hypotonia, visual impairment, epilepsy, and microcephaly.

Most individuals presented with spasticity (68%), dystonia (60%), or a combination of the two (52%).
Sources: Literature
Dystonia - complex v0.196 CHD8 Zornitza Stark Marked gene: CHD8 as ready
Dystonia - complex v0.196 CHD8 Zornitza Stark Gene: chd8 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.196 CHD8 Zornitza Stark Classified gene: CHD8 as Amber List (moderate evidence)
Dystonia - complex v0.196 CHD8 Zornitza Stark Gene: chd8 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.195 CHD8 Zornitza Stark gene: CHD8 was added
gene: CHD8 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: CHD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD8 were set to 34415117
Phenotypes for gene: CHD8 were set to Neurodevelopmental disorder, CHD8-related, MIM#615032; Dystonia
Review for gene: CHD8 was set to AMBER
Added comment: Two individuals reported with marked childhood-onset dystonia on background of neurodevelopmental issues, phenotype expansion.
Sources: Literature
Dystonia - complex v0.194 SHQ1 Zornitza Stark Marked gene: SHQ1 as ready
Dystonia - complex v0.194 SHQ1 Zornitza Stark Gene: shq1 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.194 SHQ1 Zornitza Stark Classified gene: SHQ1 as Amber List (moderate evidence)
Dystonia - complex v0.194 SHQ1 Zornitza Stark Gene: shq1 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.193 SHQ1 Zornitza Stark gene: SHQ1 was added
gene: SHQ1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: SHQ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHQ1 were set to 34542157; 29178645
Phenotypes for gene: SHQ1 were set to Dystonia; Neurodegeneration
Review for gene: SHQ1 was set to AMBER
Added comment: Three unrelated families reported. Family 1: isolated dystonia only; Family 2: dystonia, and neurodegeneration; Family 3: neurodegeneration. Rated Amber as phenotypes likely represent a continuum but currently unclear what proportion will have complex dystonia.
Sources: Literature
Dystonia - complex v0.192 IMPDH2 Arina Puzriakova reviewed gene: IMPDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34305140; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dystonia - complex v0.192 FTDALS Bryony Thompson Marked STR: FTDALS as ready
Dystonia - complex v0.192 FTDALS Bryony Thompson Str: ftdals has been classified as Green List (High Evidence).
Dystonia - complex v0.192 FTDALS Bryony Thompson Classified STR: FTDALS as Green List (high evidence)
Dystonia - complex v0.192 FTDALS Bryony Thompson Str: ftdals has been classified as Green List (High Evidence).
Dystonia - complex v0.191 FTDALS Bryony Thompson STR: FTDALS was added
STR: FTDALS was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for STR: FTDALS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FTDALS were set to 26166205; 24363131; 26187722; 25577942; 21944779; 21944778
Phenotypes for STR: FTDALS were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MIM#105550
Review for STR: FTDALS was set to GREEN
STR: FTDALS was marked as clinically relevant
Added comment: NG_031977​.1:g.5321GGGGCC[X]
Repeat expansion affects the protein degradation pathways and may contribute to TDP‐43 accumulation
Normal alleles: ≤25 G4C2 hexanucleotide repeat units generally considered normal
Pathogenic high-penetrance alleles: ≥60 G4C2 hexanucleotide repeat units are considered pathogenic
Note: The minimal size of a G4C2 pathogenic repeat is under debate: some studies consider repeats of >30 G4C2 hexanucleotide repeat units as pathogenic, whereas others use a cutoff of 60 G4C2 hexanucleotide repeat units.
Sources: Expert list
Dystonia - complex v0.190 Bryony Thompson removed STR:C9orf72 from the panel
Dystonia - complex v0.189 RNU7-1 Zornitza Stark Marked gene: RNU7-1 as ready
Dystonia - complex v0.189 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Dystonia - complex v0.189 RNU7-1 Zornitza Stark Phenotypes for gene: RNU7-1 were changed from Aicardi–Goutières syndrome-like to Aicardi-Goutieres syndrome 9, MIM# 619487
Dystonia - complex v0.188 RNU7-1 Zornitza Stark reviewed gene: RNU7-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 9, MIM# 619487; Mode of inheritance: None
Dystonia - complex v0.188 CAMK4 Zornitza Stark edited their review of gene: CAMK4: Changed phenotypes: Intellectual disability, Autism, Behavioral abnormality, Abnormality of movement, Dystonia, Ataxia, Chorea, Myoclonus
Dystonia - complex v0.188 CAMK4 Zornitza Stark Marked gene: CAMK4 as ready
Dystonia - complex v0.188 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Dystonia - complex v0.188 CAMK4 Zornitza Stark Phenotypes for gene: CAMK4 were changed from 30262571; 33098801; 33211350 to Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus
Dystonia - complex v0.187 CAMK4 Zornitza Stark Classified gene: CAMK4 as Green List (high evidence)
Dystonia - complex v0.187 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Dystonia - complex v0.186 CAMK4 Zornitza Stark gene: CAMK4 was added
gene: CAMK4 was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: CAMK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Phenotypes for gene: CAMK4 were set to 30262571; 33098801; 33211350
Review for gene: CAMK4 was set to GREEN
Added comment: 3 publications by Zech et al (2018, 2020 - PMIDs : 30262571, 33098801, 33211350) provide clinical details on 3 individuals, each harboring a private de novo CAMK4 variant.

Overlapping features included DD, ID, behavoral issues, autism and abnormal hyperkinetic movements. Dystonia and chorea in all 3 appeared 3-20 years after initial symptoms.

CAMK4 encodes Calcium/Calmodulin-dependent protein kinase IV, an important mediator of calcium-mediated activity and dynamics, particularly in the brain. It is involved in neuronal transmission, synaptic plasticity, and neuronal gene expression required for brain development and neuronal homeostasis (summary by OMIM based on Zech et al, 2018).

The 473 aa enzyme has a protein kinase domain (aa 46-300) and a C-terminal autoregulatory domain (aa 305-341) the latter comprising an autoinhibitory domain (AID / aa 305-321) and a calmodulin-binding domain (CBD / aa 322-341) [NP_001735.1 / NM_001744.4 - also used below].

Variants in all 3 subjects were identified following trio-WES and were in all cases protein-truncating, mapping to exon 10 or exon 10-intron 10 junction, expected to escape NMD and cause selective abrogation of the autoinhibitory domain (aa 305-321) leading overall to gain-of-function.

Variation databases include pLoF CAMK4 variants albeit in all cases usptream or downstream of this region (pLI of this gene in gnomAD: 0.51). Variants leading to selective abrogation of the autoregulatory domain have not been reported.

Extensive evidence for the GoF effect of the variant has been provided in the first publication. Several previous studies have demonstrated that abrogation of the AID domain leads to consitutive activation (details below).

Mouse models - though corresponding to homozygous loss of function - support a role for CAMKIV in cognitive and motor symptoms. Null mice display tremulous and ataxic movements, deficiencies in balance and sensorimotor performance associated with reduced number of Purkinje neurons (Ribar et al 2000, PMID: 11069976 - not reviewed). Wei et al (2002, PMID: 12006982 - not reviewed) provided evidence for alteration in hippocampal physiology and memory function.

Heterozygous mutations in other genes for calcium/calmodulin-dependent protein kinases (CAMKs) e.g. CAMK2A/CAMK2B (encoding subunits of CAMKII) have been reported in individuals with ID.

---

The proband in the first publication (PMID: 30262571) was a male with DD, ID, behavioral difficulties (ASD, autoaggression, stereotypies) and hyperkinetic movement disorder (myoclonus, chorea, ataxia) with severe generalized dystonia (onset at the age of 13y). Brain MRI demonstrated cerebellar atrophy.

Extensive work-up incl. karyotyping, CMA, DYT-TOR1A, THAP1, GCH1, SCA1/2/3/6/7/8/12/17, Friedreich's ataxia and FMR1 analysis was negative.F

Trio WES identified a dn splice site variant (c.981+1G>A) in the last exon-intron junction. RT-PCR followed by gel electrophoresis and Sanger in fibroblasts from an affected and control subject revealed that the proband had - as predicted by the type/location of the variant - in equal amount 2 cDNA products, a normal as well as a truncated one.

Sequencing of the shortest revealed utilization of a cryptic donor splice site upstream of the mutated donor leading to a 77bp out-of-frame deletion and introduction of a premature stop codon in the last codon (p.Lys303Serfs*28). Western blot in fibroblast cell lines revealed 2 bands corresponding to the normal protein product as well as to the p.Lys303Serfs*28 although expression of the latter was lower than that of the full length protein.

Several previous studies have shown that mutant CAMKIV species that lack the autoinhibitory domain are consitutively active (several Refs provided). Among others Chatila et al (1996, PMID: 8702940) studied an in vitro-engineered truncation mutant (Δ1-317 - truncation at position 317 of the protein) with functionally validated gain-of-function effect.

To prove enhanced activity of the splicing variant, Zech et al assessed phosphorylation of CREB (cyclic AMP-responsive element binding protein), a downstream substrate of CAMKIV. Immunobloting revealed significant increase of CREB phosphorylation in patient fibroblasts compared to controls. Overactivation of CAMKIV signaling was reversed when cells were treated with STO-609 an inhibitor of CAMKK, the ustream activator of CAMKIV.

Overall the authors demonstrated that loss of CAMKIV autoregulatory domain due to this splice variant had a gain-of-function effect.

----

Following trio-WES, Zech et al (2020 - PMID: 33098801) identified another relevant subject within cohort of 764 individuals with dystonia. This 12-y.o. male, harboring a different variant affecting the same donor site (c.981+1G>T), presented DD, ID, dystonia (onset at 3y) and additional movement disorders (myoclonus, ataxia) as well as similar behavior (ASD, autoaggression, stereotypies). [Details in suppl. p20].

----

Finally Zech et al (2020 - PMID: 33211350) reported on a 24-y.o. woman with adolescence onset choreodystonia. Other features included DD, moderate ID, absence seizures in infancy, OCD with anxiety and later diagnosis of ASD. Trio WES revealed a dn stopgain variant (c.940C>T; p.Gln314*).
Sources: Expert Review
Dystonia - complex v0.185 IMPDH2 Zornitza Stark Marked gene: IMPDH2 as ready
Dystonia - complex v0.185 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Dystonia - complex v0.185 IMPDH2 Zornitza Stark Phenotypes for gene: IMPDH2 were changed from Dystonia to Neurodevelopmental disorder with dystonia
Dystonia - complex v0.184 IMPDH2 Zornitza Stark Classified gene: IMPDH2 as Green List (high evidence)
Dystonia - complex v0.184 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Dystonia - complex v0.183 IMPDH2 Laura Raiti gene: IMPDH2 was added
gene: IMPDH2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPDH2 were set to PMID: 33098801
Phenotypes for gene: IMPDH2 were set to Dystonia
Review for gene: IMPDH2 was set to GREEN
Added comment: 6 unrelated individuals
1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein.
IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition.
1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified:
3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg)
1 x deletion: c.478_480delTCC (p.Ser160del)
The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair.
The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1.

The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2.
Sources: Literature
Dystonia - complex v0.183 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Dystonia - complex v0.182 VPS41 Zornitza Stark edited their review of gene: VPS41: Changed phenotypes: Spinocerebellar ataxia-29 (SCAR29), MIM#619389, Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Dystonia - complex v0.182 EIF2AK2 Zornitza Stark Publications for gene: EIF2AK2 were set to 33236446
Dystonia - complex v0.181 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Green List (high evidence)
Dystonia - complex v0.181 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Dystonia - complex v0.180 EIF2AK2 Zornitza Stark edited their review of gene: EIF2AK2: Changed rating: GREEN
Dystonia - complex v0.180 EIF2AK2 Zornitza Stark edited their review of gene: EIF2AK2: Added comment: PMID 33866603: further report of dystonia in a 3-generation family, same variant (p.Gly130Arg); Changed publications: 33236446, 33866603
Dystonia - complex v0.180 UBTF Zornitza Stark Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; MONDO:0044701
Dystonia - complex v0.179 UBTF Zornitza Stark reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672, MONDO:0044701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.179 VPS41 Zornitza Stark Publications for gene: VPS41 were set to 32808683
Dystonia - complex v0.178 VPS41 Zornitza Stark Classified gene: VPS41 as Green List (high evidence)
Dystonia - complex v0.178 VPS41 Zornitza Stark Gene: vps41 has been classified as Green List (High Evidence).
Dystonia - complex v0.177 VPS41 Zornitza Stark edited their review of gene: VPS41: Added comment: Another 9 individuals from 5 unrelated families reported. Affected individuals were born after uneventful pregnancies and presented in most cases early in life with developmental delay. Various degrees of ataxia, hypotonia, and dystonia were present in all affected individuals, preventing independent ambulation. Likewise, nystagmus was commonly described. In addition, all affected individuals displayed intellectual disability and speech delay, and one sib pair had treatment-resistant epilepsy.; Changed rating: GREEN; Changed publications: 32808683, 33764426
Dystonia - complex v0.177 VPS16 Zornitza Stark Phenotypes for gene: VPS16 were changed from Dystonia to Dystonia 30, MIM#619291
Dystonia - complex v0.176 VPS16 Zornitza Stark edited their review of gene: VPS16: Changed phenotypes: Dystonia 30, MIM#619291
Dystonia - complex v0.176 COQ8A Zornitza Stark Marked gene: COQ8A as ready
Dystonia - complex v0.176 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Dystonia - complex v0.176 COQ8A Zornitza Stark Classified gene: COQ8A as Green List (high evidence)
Dystonia - complex v0.176 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Dystonia - complex v0.175 COQ8A Zornitza Stark gene: COQ8A was added
gene: COQ8A was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8A were set to 32337771
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4, MIM# 612016
Review for gene: COQ8A was set to GREEN
Added comment: PMID 32337771: cohort of 59 individuals. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms.
Sources: Expert list
Dystonia - complex v0.174 MECR Zornitza Stark Phenotypes for gene: MECR were changed from Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM#617282 to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282; MONDO:0015003
Dystonia - complex v0.173 MECR Zornitza Stark Publications for gene: MECR were set to PMID: 27817865; 31137067
Dystonia - complex v0.172 MECR Zornitza Stark reviewed gene: MECR: Rating: GREEN; Mode of pathogenicity: None; Publications: 27817865, 33401012, 31137067, 31070877; Phenotypes: Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282, MONDO:0015003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.172 VPS4A Zornitza Stark Phenotypes for gene: VPS4A were changed from Neurodevelopmental disorder to CIMDAG syndrome MIM# 619273
Dystonia - complex v0.171 VPS4A Zornitza Stark reviewed gene: VPS4A: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: CIMDAG syndrome MIM# 619273; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.171 MED27 Zornitza Stark reviewed gene: MED27: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, MIM# 619286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.171 TSPOAP1 Tiong Tan gene: TSPOAP1 was added
gene: TSPOAP1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSPOAP1 were set to 33539324
Phenotypes for gene: TSPOAP1 were set to dystonia; intellectual disability; cerebellar atrophy
Penetrance for gene: TSPOAP1 were set to Complete
Review for gene: TSPOAP1 was set to GREEN
Added comment: Sources: Literature
Dystonia - complex v0.170 MED27 Alison Yeung Classified gene: MED27 as Green List (high evidence)
Dystonia - complex v0.170 MED27 Alison Yeung Gene: med27 has been classified as Green List (High Evidence).
Dystonia - complex v0.169 MED27 Alison Yeung gene: MED27 was added
gene: MED27 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 33443317
Phenotypes for gene: MED27 were set to Intellectual disability; cerebellar hypoplasia; dystonia
Review for gene: MED27 was set to GREEN
gene: MED27 was marked as current diagnostic
Added comment: 16 patients from 11 families reported
Sources: Literature
Dystonia - complex v0.168 NR4A2 Sebastian Lunke Marked gene: NR4A2 as ready
Dystonia - complex v0.168 NR4A2 Sebastian Lunke Gene: nr4a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.168 NR4A2 Sebastian Lunke Classified gene: NR4A2 as Green List (high evidence)
Dystonia - complex v0.168 NR4A2 Sebastian Lunke Gene: nr4a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.167 NR4A2 Sebastian Lunke gene: NR4A2 was added
gene: NR4A2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NR4A2 were set to 31922365
Phenotypes for gene: NR4A2 were set to Intellectual Disability; Dystonia and Early-onset Parkinson
Review for gene: NR4A2 was set to GREEN
Added comment: Three patients described to expand the known phenotype of mild ID with early adulthood onset Dystonia and Early-onset Parkinson. Three patients described in two publications, two with frameshift and one with missense, all de-novo.

https://doi.org/10.1212/NXG.0000000000000543
https://doi.org/10.1002/mds.27982
Sources: Literature
Dystonia - complex v0.166 KIF1A Bryony Thompson Classified gene: KIF1A as Green List (high evidence)
Dystonia - complex v0.166 KIF1A Bryony Thompson Gene: kif1a has been classified as Green List (High Evidence).
Dystonia - complex v0.165 KIF1A Bryony Thompson gene: KIF1A was added
gene: KIF1A was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: KIF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF1A were set to 32096284; 32935419
Phenotypes for gene: KIF1A were set to Dystonia; spastic paraplegia; intellectual disability
Review for gene: KIF1A was set to GREEN
gene: KIF1A was marked as current diagnostic
Added comment: Dystonia was a feature of the phenotype in 4/10 cases with de novo or parental germline mosaic variants.
Sources: Literature
Dystonia - complex v0.163 ZNF526 Zornitza Stark Marked gene: ZNF526 as ready
Dystonia - complex v0.163 ZNF526 Zornitza Stark Gene: znf526 has been classified as Green List (High Evidence).
Dystonia - complex v0.163 ZNF526 Zornitza Stark Classified gene: ZNF526 as Green List (high evidence)
Dystonia - complex v0.163 ZNF526 Zornitza Stark Gene: znf526 has been classified as Green List (High Evidence).
Dystonia - complex v0.162 ZNF526 Zornitza Stark gene: ZNF526 was added
gene: ZNF526 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: ZNF526 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF526 were set to 21937992; 25558065; 33397746
Phenotypes for gene: ZNF526 were set to Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia
Review for gene: ZNF526 was set to GREEN
Added comment: - PMID: 21937992 (2011) - Two unrelated families (with 4 affected individuals in each) with non-syndromic ID (mild or moderate, respectively) identified harbouring different biallelic missense variants in the ZNF526 gene.

- PMID: 25558065 (2015) - One family with ID, Noonan-like facies, pulmonary stenosis and a homozygous missense variant in this gene. No further details provided.

- PMID: 33397746 (2021) - Five individuals from four unrelated families with homozygous ZNF526 variants. Four harboured truncating variants, and were all affected by profound DD and severe ID, microcephaly (ranging from -4 SD to -8 SD), bilateral progressive cataracts, hypertonic-dystonic movements, epilepsy and brain MRI anomalies. The fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (-2 SD), progressive bilateral cataracts, severe ID, and normal brain MRI. Zebrafish model demonstrated brain and eye malformations resembling findings seen in the human holoprosencephaly spectrum
Sources: Literature
Dystonia - complex v0.161 EIF2AK2 Zornitza Stark Marked gene: EIF2AK2 as ready
Dystonia - complex v0.161 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.161 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Amber List (moderate evidence)
Dystonia - complex v0.161 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.160 EIF2AK2 Zornitza Stark gene: EIF2AK2 was added
gene: EIF2AK2 was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to 33236446
Phenotypes for gene: EIF2AK2 were set to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness; early onset dystonia
Review for gene: EIF2AK2 was set to AMBER
Added comment: 10 individuals reported with complex neurological phenotype including ataxia and spasticity.

Additional report in PMID 33236446 of same missense variant, p.Gly130Arg segregating with disease in 5 individuals from one family, and occurring de novo in another individual with prominent, early-onset dystonia. One more individual identified with a homozygous variant and dystonia. Some functional data to support variant pathogenicity. Three of the individuals had additional neurological features including ID.
Sources: Expert Review
Dystonia - complex v0.159 RNU7-1 Sue White Classified gene: RNU7-1 as Green List (high evidence)
Dystonia - complex v0.159 RNU7-1 Sue White Gene: rnu7-1 has been classified as Green List (High Evidence).
Dystonia - complex v0.158 RNU7-1 Paul De Fazio gene: RNU7-1 was added
gene: RNU7-1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to 33230297
Phenotypes for gene: RNU7-1 were set to Aicardi–Goutières syndrome-like
Review for gene: RNU7-1 was set to GREEN
gene: RNU7-1 was marked as current diagnostic
Added comment: Review originally submitted by Ming Wong
- 16 affected individuals from 11 families
- Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of
replication-dependent histone (RDH) mRNAs
Sources: Literature
Dystonia - complex v0.158 YIF1B Zornitza Stark Phenotypes for gene: YIF1B were changed from Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement to Kaya-Barakat-Masson syndrome, MIM# 619125; Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Dystonia - complex v0.157 YIF1B Zornitza Stark edited their review of gene: YIF1B: Changed phenotypes: Kaya-Barakat-Masson syndrome, MIM# 619125, Central hypotonia, Failure to thrive, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Spasticity, Abnormality of movement
Dystonia - complex v0.157 VPS4A Elena Savva Deleted their review
Dystonia - complex v0.157 VPS4A Elena Savva Marked gene: VPS4A as ready
Dystonia - complex v0.157 VPS4A Elena Savva Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Dystonia - complex v0.157 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Dystonia - complex v0.157 VPS4A Elena Savva Added comment: Comment on mode of pathogenicity: Dominant negative
Dystonia - complex v0.157 VPS4A Elena Savva Mode of pathogenicity for gene: VPS4A was changed from None to Other
Dystonia - complex v0.156 VPS4A Elena Savva Classified gene: VPS4A as Green List (high evidence)
Dystonia - complex v0.156 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Dystonia - complex v0.155 VPS4A Kristin Rigbye gene: VPS4A was added
gene: VPS4A was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to 33186543; 33186545
Phenotypes for gene: VPS4A were set to Neurodevelopmental disorder
Review for gene: VPS4A was set to GREEN
Added comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.

"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Sources: Literature
Dystonia - complex v0.155 MOGS Zornitza Stark Marked gene: MOGS as ready
Dystonia - complex v0.155 MOGS Zornitza Stark Gene: mogs has been classified as Red List (Low Evidence).
Dystonia - complex v0.155 MOGS Zornitza Stark gene: MOGS was added
gene: MOGS was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: MOGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOGS were set to 33058492
Phenotypes for gene: MOGS were set to Congenital disorder of glycosylation, type IIb, MIM# 606056
Review for gene: MOGS was set to RED
Added comment: 7 individuals from 6 unrelated families reported with CDGIIb. Of these, one had prominent dystonia, with forced posture of the head and of both hands, as well as a hyperkinetic movement disorder.
Sources: Expert Review
Dystonia - complex v0.154 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from hypotonia; severe intellectual disability; dyskinesia; dysmorphism to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Dystonia - complex v0.153 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.153 ALK Zornitza Stark Marked gene: ALK as ready
Dystonia - complex v0.153 ALK Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.153 ALK Zornitza Stark Classified gene: ALK as Amber List (moderate evidence)
Dystonia - complex v0.153 ALK Zornitza Stark Gene: alk has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.152 ALK Dean Phelan gene: ALK was added
gene: ALK was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALK were set to PMID: 32989326
Phenotypes for gene: ALK were set to Spastic-dystonic diplegia
Review for gene: ALK was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two patients with spastic diplegia with mild tremor, scattered subcortical hyperintensities and an atrial septal defect; and spastic-dystonic diplegia, white matter abnormalities and epilepsy, respectively, with no evidence of neuroblastoma in either patient
Sources: Literature
Dystonia - complex v0.152 C9orf72 Bryony Thompson Classified gene: C9orf72 as No list
Dystonia - complex v0.152 C9orf72 Bryony Thompson Gene: c9orf72 has been removed from the panel.
Dystonia - complex v0.151 C9orf72 Bryony Thompson Marked STR: C9orf72 as ready
Dystonia - complex v0.151 C9orf72 Bryony Thompson Str: c9orf72 has been classified as Green List (High Evidence).
Dystonia - complex v0.151 C9orf72 Bryony Thompson Classified STR: C9orf72 as Green List (high evidence)
Dystonia - complex v0.151 C9orf72 Bryony Thompson Str: c9orf72 has been classified as Green List (High Evidence).
Dystonia - complex v0.150 C9orf72 Bryony Thompson STR: C9orf72 was added
STR: C9orf72 was added to Dystonia - complex. Sources: Expert list
STR tags were added to STR: C9orf72.
Mode of inheritance for STR: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: C9orf72 were set to 26166205; 24363131; 26187722; 25577942
Phenotypes for STR: C9orf72 were set to Dystonia; Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MIM#105550
Review for STR: C9orf72 was set to GREEN
STR: C9orf72 was marked as clinically relevant
Added comment: NG_031977​.1:g.5321GGGGCC[X]
Repeat expansion affects the protein degradation pathways and may contribute to TDP‐43 accumulation
Normal alleles: ≤25 G4C2 hexanucleotide repeat units generally considered normal
Pathogenic high-penetrance alleles: ≥60 G4C2 hexanucleotide repeat units are considered pathogenic
Note: The minimal size of a G4C2 pathogenic repeat is under debate: some studies consider repeats of >30 G4C2 hexanucleotide repeat units as pathogenic, whereas others use a cutoff of 60 G4C2 hexanucleotide repeat units.
Sources: Expert list
Dystonia - complex v0.149 VPS41 Zornitza Stark Marked gene: VPS41 as ready
Dystonia - complex v0.149 VPS41 Zornitza Stark Gene: vps41 has been classified as Red List (Low Evidence).
Dystonia - complex v0.149 VPS41 Zornitza Stark gene: VPS41 was added
gene: VPS41 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32808683
Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability
Review for gene: VPS41 was set to RED
Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.
Sources: Literature
Dystonia - complex v0.148 VPS16 Zornitza Stark Marked gene: VPS16 as ready
Dystonia - complex v0.148 VPS16 Zornitza Stark Gene: vps16 has been classified as Green List (High Evidence).
Dystonia - complex v0.148 VPS16 Zornitza Stark Classified gene: VPS16 as Green List (high evidence)
Dystonia - complex v0.148 VPS16 Zornitza Stark Gene: vps16 has been classified as Green List (High Evidence).
Dystonia - complex v0.147 VPS16 Zornitza Stark gene: VPS16 was added
gene: VPS16 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: VPS16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS16 were set to 32808683
Phenotypes for gene: VPS16 were set to Dystonia
Review for gene: VPS16 was set to GREEN
Added comment: 18 individuals reported with high-impact variants in VPS16 and a progressive early onset dystonia (median age 12 years, range 3–50 years), with prominent oromandibular, bulbar, cervical, and upper limb involvement. Progressive generalization ensued, although most remained ambulant, and only a minority (16%) lost the ability to walk in adulthood.

Additional clinical features of mild to moderate intellectual disability and neuropsychiatric symptoms were present in approximately one‐third. In 4 individuals, magnetic resonance imaging (MRI) showed bilateral and symmetrical hypointensity of the globi pallidi and sometimes also the midbrain and dentate nuclei, suggestive of iron deposition. Mild generalized cerebral atrophy was also apparent in 4 individuals.
Sources: Literature
Dystonia - complex v0.146 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Dystonia - complex v0.146 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Dystonia - complex v0.146 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Dystonia - complex v0.146 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Dystonia - complex v0.145 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Dystonia - complex v0.144 RHOBTB2 Zornitza Stark Marked gene: RHOBTB2 as ready
Dystonia - complex v0.144 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Dystonia - complex v0.144 RHOBTB2 Zornitza Stark Phenotypes for gene: RHOBTB2 were changed from Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy to Epileptic encephalopathy, early infantile, 64, MIM# 618004; Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy
Dystonia - complex v0.143 RHOBTB2 Zornitza Stark Classified gene: RHOBTB2 as Green List (high evidence)
Dystonia - complex v0.143 RHOBTB2 Zornitza Stark Gene: rhobtb2 has been classified as Green List (High Evidence).
Dystonia - complex v0.142 RHOBTB2 Eunice Chan gene: RHOBTB2 was added
gene: RHOBTB2 was added to Dystonia - complex. Sources: Other
Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RHOBTB2 were set to PMID: 29276004
Phenotypes for gene: RHOBTB2 were set to Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy
Added comment: 8/10 patients described had dystonic, paroxysmal, or chorea-like movements
Sources: Other
Dystonia - complex v0.142 VAMP1 Zornitza Stark Classified gene: VAMP1 as Amber List (moderate evidence)
Dystonia - complex v0.142 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.141 VAMP1 Zornitza Stark Tag founder tag was added to gene: VAMP1.
Dystonia - complex v0.141 VAMP1 Zornitza Stark edited their review of gene: VAMP1: Added comment: Single variant reported in four Newfoundland families, founder effect.; Changed rating: AMBER; Changed phenotypes: Spastic ataxia 1, autosomal dominant, MIM# 108600
Dystonia - complex v0.140 ATP7B Zornitza Stark Marked gene: ATP7B as ready
Dystonia - complex v0.140 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Dystonia - complex v0.140 ATP7B Zornitza Stark Phenotypes for gene: ATP7B were changed from Wilson disease 277900; Dystonia to Wilson disease, MIM# 277900; Dystonia
Dystonia - complex v0.139 ATP7B Zornitza Stark Publications for gene: ATP7B were set to
Dystonia - complex v0.138 ATP7B Zornitza Stark reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32662046; Phenotypes: Wilson disease, MIM# 277900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.138 VPS13D Zornitza Stark Marked gene: VPS13D as ready
Dystonia - complex v0.138 VPS13D Zornitza Stark Gene: vps13d has been classified as Green List (High Evidence).
Dystonia - complex v0.138 VPS13D Zornitza Stark Classified gene: VPS13D as Green List (high evidence)
Dystonia - complex v0.138 VPS13D Zornitza Stark Gene: vps13d has been classified as Green List (High Evidence).
Dystonia - complex v0.137 VPS13D Zornitza Stark gene: VPS13D was added
gene: VPS13D was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: VPS13D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13D were set to 29604224; 29518281
Phenotypes for gene: VPS13D were set to Spinocerebellar ataxia, autosomal recessive 4, MIM# 607317
Review for gene: VPS13D was set to GREEN
Added comment: 7 unrelated families reported and a mouse model. Most affected individuals have ataxic gait with spasticity and hyperreflexia of the lower limbs resulting in difficulty walking. The age at onset is highly variable: some have onset in early childhood with delayed walking, whereas others have onset of gait difficulties in adulthood. Additional features may include dysarthria, oculomotor abnormalities, distal sensory impairment, dystonia, chorea, hypotonia, pyramidal signs, and cerebellar atrophy on brain imaging. The disorder is slowly progressive. Some individuals with onset in childhood may have global developmental delay with mild intellectual disability.
Sources: Expert list
Dystonia - complex v0.136 VAMP2 Zornitza Stark Marked gene: VAMP2 as ready
Dystonia - complex v0.136 VAMP2 Zornitza Stark Gene: vamp2 has been classified as Green List (High Evidence).
Dystonia - complex v0.136 VAMP2 Zornitza Stark Classified gene: VAMP2 as Green List (high evidence)
Dystonia - complex v0.136 VAMP2 Zornitza Stark Gene: vamp2 has been classified as Green List (High Evidence).
Dystonia - complex v0.135 VAMP2 Zornitza Stark gene: VAMP2 was added
gene: VAMP2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: VAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VAMP2 were set to 30929742
Phenotypes for gene: VAMP2 were set to Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements 618760; Dystonia; Cortical visual impairment; Seizures; Stereotypic behaviour; Generalized hypotonia; Intellectual disability
Review for gene: VAMP2 was set to GREEN
Added comment: 5 unrelated patients with heterozygous de novo mutations in VAMP2, presenting with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The abnormal movements included dystonia.
Sources: Expert list
Dystonia - complex v0.134 VAMP1 Zornitza Stark Marked gene: VAMP1 as ready
Dystonia - complex v0.134 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Dystonia - complex v0.134 VAMP1 Zornitza Stark Classified gene: VAMP1 as Green List (high evidence)
Dystonia - complex v0.134 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Dystonia - complex v0.133 VAMP1 Zornitza Stark gene: VAMP1 was added
gene: VAMP1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: VAMP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VAMP1 were set to 22958904
Phenotypes for gene: VAMP1 were set to Spastic ataxia 1, autosomal dominant, MIM# 108600
Review for gene: VAMP1 was set to GREEN
Added comment: Autosomal dominant neurodegenerative disorder characterised by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance. Onset is between the ages of 10 and 20 years. Other clinical features are supranuclear gaze palsy, hyperreflexia, hypertonicity, dystonia, pes cavus, mild ptosis, and decreased vibration sense in the lower limbs.
Sources: Expert list
Dystonia - complex v0.132 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Dystonia - complex v0.132 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Dystonia - complex v0.132 SURF1 Zornitza Stark Classified gene: SURF1 as Green List (high evidence)
Dystonia - complex v0.132 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Dystonia - complex v0.131 SURF1 Zornitza Stark gene: SURF1 was added
gene: SURF1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: SURF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SURF1 were set to 19780766
Phenotypes for gene: SURF1 were set to Leigh syndrome, due to COX IV deficiency, MIM# 256000
Review for gene: SURF1 was set to GREEN
Added comment: SURF1 gene mutations are the most common cause of Leigh syndrome (LS), a progressive neurodegenerative disorder of infancy, characterised by symmetric necrotizing lesions and hypervascularity in the brainstem and basal ganglia. Dystonia is part of the phenotype, particularly in those with milder phenotypes/missense variants.
Sources: Expert list
Dystonia - complex v0.130 SQSTM1 Zornitza Stark Phenotypes for gene: SQSTM1 were changed from Myopathy, distal, with rimmed vacuoles 617158 to Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145
Dystonia - complex v0.129 SQSTM1 Zornitza Stark reviewed gene: SQSTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.129 SLC20A2 Zornitza Stark Marked gene: SLC20A2 as ready
Dystonia - complex v0.129 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.129 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to
Dystonia - complex v0.128 SLC20A2 Zornitza Stark reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22327515, 23334463, 24411498; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.128 SLC16A2 Zornitza Stark changed review comment from: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. Paroxysmal dystonic dyskinesia triggered by passive movements, excitement, crying reported.
Sources: Expert Review; to: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. In a recent review of 24 affected individuals (PMID 31410843), 16 presented with profound developmental delay, three had severe intellectual disability with poor language and walking with an aid, four had moderate intellectual disability with language and walking abilities, and one had mild intellectual disability with hypotonia. Overall, eight had learned to walk, all had hypotonia, 17 had spasticity, 18 had dystonia, 12 had choreoathetosis, 19 had hypomyelination, and 10 had brain atrophy. Kyphoscoliosis (n=12), seizures (n=7), and pneumopathies (n=5) were the most severe complications. Paroxysmal dystonic dyskinesia triggered by passive movements, excitement, crying is reported.
Sources: Expert Review
Dystonia - complex v0.128 SLC16A2 Zornitza Stark Marked gene: SLC16A2 as ready
Dystonia - complex v0.128 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.128 SLC16A2 Zornitza Stark Classified gene: SLC16A2 as Green List (high evidence)
Dystonia - complex v0.128 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.127 SLC16A2 Zornitza Stark gene: SLC16A2 was added
gene: SLC16A2 was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC16A2 were set to 15980113; 31410843; 20301789
Phenotypes for gene: SLC16A2 were set to Allan-Herndon-Dudley syndrome, MIM# 300523
Review for gene: SLC16A2 was set to GREEN
Added comment: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. Paroxysmal dystonic dyskinesia triggered by passive movements, excitement, crying reported.
Sources: Expert Review
Dystonia - complex v0.126 OPA3 Zornitza Stark Marked gene: OPA3 as ready
Dystonia - complex v0.126 OPA3 Zornitza Stark Gene: opa3 has been classified as Green List (High Evidence).
Dystonia - complex v0.126 OPA3 Zornitza Stark Phenotypes for gene: OPA3 were changed from developmental delay, hypotonia; dystonia and chorea; ataxia, optic atrophy; spastic paraplegia to 3-methylglutaconic aciduria, type III, MIM# 258501; developmental delay, hypotonia; dystonia and chorea; ataxia, optic atrophy; spastic paraplegia
Dystonia - complex v0.125 OPA3 Zornitza Stark Publications for gene: OPA3 were set to PMID: 20301646
Dystonia - complex v0.124 OPA3 Zornitza Stark Classified gene: OPA3 as Green List (high evidence)
Dystonia - complex v0.124 OPA3 Zornitza Stark Gene: opa3 has been classified as Green List (High Evidence).
Dystonia - complex v0.123 OPA3 Zornitza Stark reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7510656, 2494568, 11668429; Phenotypes: 3-methylglutaconic aciduria, type III, MIM# 258501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.123 OPA3 Eunice Chan gene: OPA3 was added
gene: OPA3 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: OPA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OPA3 were set to PMID: 20301646
Phenotypes for gene: OPA3 were set to developmental delay, hypotonia; dystonia and chorea; ataxia, optic atrophy; spastic paraplegia
Added comment: Costeff syndrome, most patients are Iraqi-Jewish ancestry
Sources: Expert list
Dystonia - complex v0.123 SETX Zornitza Stark Marked gene: SETX as ready
Dystonia - complex v0.123 SETX Zornitza Stark Gene: setx has been classified as Green List (High Evidence).
Dystonia - complex v0.123 SETX Zornitza Stark Classified gene: SETX as Green List (high evidence)
Dystonia - complex v0.123 SETX Zornitza Stark Gene: setx has been classified as Green List (High Evidence).
Dystonia - complex v0.122 SETX Zornitza Stark gene: SETX was added
gene: SETX was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: SETX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SETX were set to 19696032
Phenotypes for gene: SETX were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, MIM# 606002
Review for gene: SETX was set to GREEN
Added comment: Dystonia was present in around 13% in a cohort of 90 affected individuals.
Sources: Expert list
Dystonia - complex v0.121 PSEN1 Zornitza Stark Marked gene: PSEN1 as ready
Dystonia - complex v0.121 PSEN1 Zornitza Stark Gene: psen1 has been classified as Green List (High Evidence).
Dystonia - complex v0.121 PSEN1 Zornitza Stark Phenotypes for gene: PSEN1 were changed from Frontotemporal dementia; Dystonia to Frontotemporal dementia, MIM# 600274; Dystonia
Dystonia - complex v0.120 PSEN1 Zornitza Stark Classified gene: PSEN1 as Green List (high evidence)
Dystonia - complex v0.120 PSEN1 Zornitza Stark Gene: psen1 has been classified as Green List (High Evidence).
Dystonia - complex v0.119 PSEN1 Zornitza Stark changed review comment from: Variants in this gene are typically associated with Alzheimer's disease and other dementias. One case report of a primary presentation with Parkinsonism-dystonia, later complicated by dementia.; to: Variants in this gene are typically associated with Alzheimer's disease and other dementias but there are reports of complex movement disorders preceding or as part of dementia presentations.
Dystonia - complex v0.119 PSEN1 Zornitza Stark edited their review of gene: PSEN1: Changed rating: GREEN; Changed publications: 12810495, 15159497, 29316780, 28664294
Dystonia - complex v0.119 PSEN1 Zornitza Stark Classified gene: PSEN1 as Red List (low evidence)
Dystonia - complex v0.119 PSEN1 Zornitza Stark Gene: psen1 has been classified as Red List (Low Evidence).
Dystonia - complex v0.118 PSEN1 Zornitza Stark reviewed gene: PSEN1: Rating: RED; Mode of pathogenicity: None; Publications: 28664294; Phenotypes: Dementia, frontotemporal, MIM# 600274; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.118 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Dystonia - complex v0.118 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Dystonia - complex v0.118 POLR3A Zornitza Stark Classified gene: POLR3A as Green List (high evidence)
Dystonia - complex v0.118 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Dystonia - complex v0.117 POLR3A Zornitza Stark gene: POLR3A was added
gene: POLR3A was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to 32600288; 32373668; 31940116; 31932101; 29618326
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; Striatal abnormalities; Dystonia
Review for gene: POLR3A was set to GREEN
Added comment: Multiple individuals reported where dystonia is part of the phenotype. Some of these have had hypomyelinating leukodystrophy, whereas others have had very prominent striatal abnormalities on MRI, in the absence of white matter changes. It is unclear whether this represents a continuum or a separate disorder.
Sources: Expert list
Dystonia - complex v0.116 PNKP Zornitza Stark Marked gene: PNKP as ready
Dystonia - complex v0.116 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Dystonia - complex v0.116 PNKP Zornitza Stark Classified gene: PNKP as Green List (high evidence)
Dystonia - complex v0.116 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Dystonia - complex v0.115 PNKP Zornitza Stark gene: PNKP was added
gene: PNKP was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: PNKP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNKP were set to 28552035; 25728773
Phenotypes for gene: PNKP were set to Ataxia-oculomotor apraxia 4, MIM# 616267
Review for gene: PNKP was set to GREEN
Added comment: Dystonia is part of this complex neurological phenotype, which also includes ataxia, oculomotor apraxia and peripheral neuropathy.
Sources: Expert list
Dystonia - complex v0.114 PDGFRB Zornitza Stark Marked gene: PDGFRB as ready
Dystonia - complex v0.114 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Red List (Low Evidence).
Dystonia - complex v0.114 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from Dystonia; Basal ganglia calcification, idiopathic, 4 615007 to Basal ganglia calcification, idiopathic, 4, MIM# 615007
Dystonia - complex v0.113 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to
Dystonia - complex v0.112 PDGFRB Zornitza Stark Classified gene: PDGFRB as Red List (low evidence)
Dystonia - complex v0.112 PDGFRB Zornitza Stark Gene: pdgfrb has been classified as Red List (Low Evidence).
Dystonia - complex v0.111 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: RED; Mode of pathogenicity: None; Publications: 24518837; Phenotypes: Basal ganglia calcification, idiopathic, MIM#4 615007; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.111 PCCB Zornitza Stark Marked gene: PCCB as ready
Dystonia - complex v0.111 PCCB Zornitza Stark Gene: pccb has been classified as Green List (High Evidence).
Dystonia - complex v0.111 PCCB Zornitza Stark Classified gene: PCCB as Green List (high evidence)
Dystonia - complex v0.111 PCCB Zornitza Stark Gene: pccb has been classified as Green List (High Evidence).
Dystonia - complex v0.110 PCCB Zornitza Stark gene: PCCB was added
gene: PCCB was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: PCCB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCCB were set to 30879957
Phenotypes for gene: PCCB were set to Propionicacidemia, MIM# 606054
Review for gene: PCCB was set to GREEN
Added comment: The neonatal form is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenia. A late-onset form in older children and adults is pertinent to this panel as it has a milder phenotype. It is less common, and may present with developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction, which may result in dystonia and choreoathetosis, and cardiomyopathy.
Sources: Expert list
Dystonia - complex v0.109 PCCA Zornitza Stark Marked gene: PCCA as ready
Dystonia - complex v0.109 PCCA Zornitza Stark Gene: pcca has been classified as Green List (High Evidence).
Dystonia - complex v0.109 PCCA Zornitza Stark Classified gene: PCCA as Green List (high evidence)
Dystonia - complex v0.109 PCCA Zornitza Stark Gene: pcca has been classified as Green List (High Evidence).
Dystonia - complex v0.108 PCCA Zornitza Stark gene: PCCA was added
gene: PCCA was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: PCCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCCA were set to 30879957
Phenotypes for gene: PCCA were set to Propionicacidemia, MIM# 606054
Review for gene: PCCA was set to GREEN
Added comment: The neonatal form is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenia. A late-onset form in older children and adults is pertinent to this panel as it has a milder phenotype. It is less common, and may present with developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction, which may result in dystonia and choreoathetosis, and cardiomyopathy.
Sources: Expert list
Dystonia - complex v0.107 KIF1C Zornitza Stark Marked gene: KIF1C as ready
Dystonia - complex v0.107 KIF1C Zornitza Stark Gene: kif1c has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.107 KIF1C Zornitza Stark Classified gene: KIF1C as Amber List (moderate evidence)
Dystonia - complex v0.107 KIF1C Zornitza Stark Gene: kif1c has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.106 KIF1C Zornitza Stark gene: KIF1C was added
gene: KIF1C was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: KIF1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF1C were set to 31413903
Phenotypes for gene: KIF1C were set to Spastic ataxia 2, autosomal recessive, MIM# 611302
Review for gene: KIF1C was set to AMBER
Added comment: Neurologic disorder characterized by onset in the first 2 decades of cerebellar ataxia, dysarthria, and variable spasticity of the lower limbs. At least one report of a more complex movement disorder including dystonia.
Sources: Expert list
Dystonia - complex v0.105 ACTB Zornitza Stark Marked gene: ACTB as ready
Dystonia - complex v0.105 ACTB Zornitza Stark Gene: actb has been classified as Green List (High Evidence).
Dystonia - complex v0.105 ACTB Zornitza Stark Mode of pathogenicity for gene: ACTB was changed from to Other
Dystonia - complex v0.104 DNAJC12 Zornitza Stark Marked gene: DNAJC12 as ready
Dystonia - complex v0.104 DNAJC12 Zornitza Stark Gene: dnajc12 has been classified as Green List (High Evidence).
Dystonia - complex v0.104 GNAO1 Zornitza Stark Marked gene: GNAO1 as ready
Dystonia - complex v0.104 GNAO1 Zornitza Stark Gene: gnao1 has been classified as Green List (High Evidence).
Dystonia - complex v0.104 GNAO1 Zornitza Stark Publications for gene: GNAO1 were set to
Dystonia - complex v0.103 GNAO1 Zornitza Stark Mode of pathogenicity for gene: GNAO1 was changed from to Other
Dystonia - complex v0.102 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
Dystonia - complex v0.102 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Dystonia - complex v0.102 PDHX Zornitza Stark Marked gene: PDHX as ready
Dystonia - complex v0.102 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Dystonia - complex v0.102 RNASEH2B Zornitza Stark Marked gene: RNASEH2B as ready
Dystonia - complex v0.102 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Dystonia - complex v0.102 RNASEH2C Zornitza Stark Marked gene: RNASEH2C as ready
Dystonia - complex v0.102 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Dystonia - complex v0.102 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Dystonia - complex v0.102 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Dystonia - complex v0.102 SUOX Zornitza Stark Marked gene: SUOX as ready
Dystonia - complex v0.102 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Dystonia - complex v0.102 SYT1 Zornitza Stark Marked gene: SYT1 as ready
Dystonia - complex v0.102 SYT1 Zornitza Stark Gene: syt1 has been classified as Green List (High Evidence).
Dystonia - complex v0.102 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Dystonia - complex v0.102 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.102 AFG3L2 Zornitza Stark Marked gene: AFG3L2 as ready
Dystonia - complex v0.102 AFG3L2 Zornitza Stark Gene: afg3l2 has been classified as Red List (Low Evidence).
Dystonia - complex v0.102 CHMP2B Zornitza Stark Marked gene: CHMP2B as ready
Dystonia - complex v0.102 CHMP2B Zornitza Stark Gene: chmp2b has been classified as Red List (Low Evidence).
Dystonia - complex v0.102 EARS2 Zornitza Stark Marked gene: EARS2 as ready
Dystonia - complex v0.102 EARS2 Zornitza Stark Gene: ears2 has been classified as Red List (Low Evidence).
Dystonia - complex v0.102 GAMT Zornitza Stark Marked gene: GAMT as ready
Dystonia - complex v0.102 GAMT Zornitza Stark Gene: gamt has been classified as Red List (Low Evidence).
Dystonia - complex v0.102 KCNQ2 Zornitza Stark Marked gene: KCNQ2 as ready
Dystonia - complex v0.102 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Red List (Low Evidence).
Dystonia - complex v0.102 MAPT Zornitza Stark Marked gene: MAPT as ready
Dystonia - complex v0.102 MAPT Zornitza Stark Gene: mapt has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.102 MAPT Zornitza Stark Classified gene: MAPT as Amber List (moderate evidence)
Dystonia - complex v0.102 MAPT Zornitza Stark Gene: mapt has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.101 MAT1A Zornitza Stark Marked gene: MAT1A as ready
Dystonia - complex v0.101 MAT1A Zornitza Stark Gene: mat1a has been classified as Red List (Low Evidence).
Dystonia - complex v0.101 MMADHC Zornitza Stark Marked gene: MMADHC as ready
Dystonia - complex v0.101 MMADHC Zornitza Stark Gene: mmadhc has been classified as Red List (Low Evidence).
Dystonia - complex v0.101 MPV17 Zornitza Stark Marked gene: MPV17 as ready
Dystonia - complex v0.101 MPV17 Zornitza Stark Gene: mpv17 has been classified as Red List (Low Evidence).
Dystonia - complex v0.101 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Dystonia - complex v0.101 PLP1 Zornitza Stark Gene: plp1 has been classified as Red List (Low Evidence).
Dystonia - complex v0.101 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Dystonia - complex v0.101 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Red List (Low Evidence).
Dystonia - complex v0.101 VPS37A Zornitza Stark Marked gene: VPS37A as ready
Dystonia - complex v0.101 VPS37A Zornitza Stark Gene: vps37a has been classified as Red List (Low Evidence).
Dystonia - complex v0.101 TOR1AIP1 Zornitza Stark Marked gene: TOR1AIP1 as ready
Dystonia - complex v0.101 TOR1AIP1 Zornitza Stark Gene: tor1aip1 has been classified as Red List (Low Evidence).
Dystonia - complex v0.101 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Dystonia - complex v0.101 UNC80 Zornitza Stark Gene: unc80 has been classified as Red List (Low Evidence).
Dystonia - complex v0.101 HPRT1 Zornitza Stark Marked gene: HPRT1 as ready
Dystonia - complex v0.101 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Green List (High Evidence).
Dystonia - complex v0.101 HPRT1 Zornitza Stark Publications for gene: HPRT1 were set to
Dystonia - complex v0.100 HPRT1 Zornitza Stark reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301328; Phenotypes: Lesch-Nyhan syndrome, MIM# 300322; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dystonia - complex v0.100 HIBCH Zornitza Stark Marked gene: HIBCH as ready
Dystonia - complex v0.100 HIBCH Zornitza Stark Gene: hibch has been classified as Green List (High Evidence).
Dystonia - complex v0.100 HIBCH Zornitza Stark Classified gene: HIBCH as Green List (high evidence)
Dystonia - complex v0.100 HIBCH Zornitza Stark Gene: hibch has been classified as Green List (High Evidence).
Dystonia - complex v0.99 HIBCH Zornitza Stark gene: HIBCH was added
gene: HIBCH was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: HIBCH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIBCH were set to 26026795; 25251209; 24299452; 32677093
Phenotypes for gene: HIBCH were set to 3-hydroxyisobutryl-CoA hydrolase deficiency, MIM# 250620
Review for gene: HIBCH was set to GREEN
Added comment: Autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia. Dystonia is a feature.
Sources: Expert Review
Dystonia - complex v0.98 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
Dystonia - complex v0.98 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Dystonia - complex v0.98 ECHS1 Zornitza Stark Classified gene: ECHS1 as Green List (high evidence)
Dystonia - complex v0.98 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Dystonia - complex v0.97 ECHS1 Zornitza Stark gene: ECHS1 was added
gene: ECHS1 was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECHS1 were set to 32677093; 32858208
Phenotypes for gene: ECHS1 were set to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277
Review for gene: ECHS1 was set to GREEN
Added comment: Paroxysmal and non-paroxysmal dystonia described as a manifestation of this metabolic disorder.
Sources: Expert Review
Dystonia - complex v0.96 GTPBP2 Zornitza Stark Marked gene: GTPBP2 as ready
Dystonia - complex v0.96 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Dystonia - complex v0.96 GTPBP2 Zornitza Stark Classified gene: GTPBP2 as Green List (high evidence)
Dystonia - complex v0.96 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Dystonia - complex v0.95 GTPBP2 Zornitza Stark gene: GTPBP2 was added
gene: GTPBP2 was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: GTPBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP2 were set to 26675814; 29449720; 30790272
Phenotypes for gene: GTPBP2 were set to Jaberi-Elahi syndrome, MIM#617988
Review for gene: GTPBP2 was set to GREEN
Added comment: Nine individuals from six unrelated families with bi-allelic variants in this gene causing a neuro-ectodermal syndrome. Key features include prenatal onset microcephaly, tone abnormalities, and movement disorders, epilepsy, dysmorphic features, retinal dysfunction, ectodermal dysplasia, and brain iron accumulation.
Sources: Expert Review
Dystonia - complex v0.94 GNB1 Zornitza Stark Marked gene: GNB1 as ready
Dystonia - complex v0.94 GNB1 Zornitza Stark Gene: gnb1 has been classified as Green List (High Evidence).
Dystonia - complex v0.94 GNB1 Zornitza Stark Phenotypes for gene: GNB1 were changed from Mental retardation, autosomal dominant 42; Myoclonus dystonia to Mental retardation, autosomal dominant 42, MIM# 616973; Myoclonus dystonia
Dystonia - complex v0.93 GNB1 Zornitza Stark Publications for gene: GNB1 were set to 30194818
Dystonia - complex v0.92 GNB1 Zornitza Stark edited their review of gene: GNB1: Changed rating: GREEN
Dystonia - complex v0.92 GNB1 Zornitza Stark reviewed gene: GNB1: Rating: RED; Mode of pathogenicity: None; Publications: 27108799, 30194818, 27668284, 31034681; Phenotypes: Mental retardation, autosomal dominant 42, MIM# 616973; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.92 GJC2 Zornitza Stark Marked gene: GJC2 as ready
Dystonia - complex v0.92 GJC2 Zornitza Stark Gene: gjc2 has been classified as Green List (High Evidence).
Dystonia - complex v0.92 GJC2 Zornitza Stark Classified gene: GJC2 as Green List (high evidence)
Dystonia - complex v0.92 GJC2 Zornitza Stark Gene: gjc2 has been classified as Green List (High Evidence).
Dystonia - complex v0.91 GJC2 Zornitza Stark gene: GJC2 was added
gene: GJC2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: GJC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GJC2 were set to 15192806; 18094336
Phenotypes for gene: GJC2 were set to Leukodystrophy, hypomyelinating, 2, MIM# 608804
Review for gene: GJC2 was set to GREEN
Added comment: Complex CNS involvement manifesting as nystagmus, impaired motor development, ataxia, choreoathetotic movements, dystonia, dysarthria, and progressive spasticity, in addition to intellectual disability. Multiple families reported.
Sources: Expert list
Dystonia - complex v0.90 GBA Zornitza Stark Marked gene: GBA as ready
Dystonia - complex v0.90 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Dystonia - complex v0.90 GBA Zornitza Stark Classified gene: GBA as Green List (high evidence)
Dystonia - complex v0.90 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Dystonia - complex v0.89 GBA Zornitza Stark gene: GBA was added
gene: GBA was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to 27789132
Phenotypes for gene: GBA were set to Gaucher disease, type III, MIM# 231000
Review for gene: GBA was set to GREEN
Added comment: Dystonia-like hyperkinetic movement disorder reported in GD3.
Sources: Expert list
Dystonia - complex v0.88 FOXG1 Zornitza Stark Marked gene: FOXG1 as ready
Dystonia - complex v0.88 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Dystonia - complex v0.88 FOXG1 Zornitza Stark Publications for gene: FOXG1 were set to
Dystonia - complex v0.87 FOXG1 Zornitza Stark reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27029630; Phenotypes: Rett syndrome, congenital variant, MIM# 613454; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.87 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Dystonia - complex v0.87 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Dystonia - complex v0.87 CYP27A1 Zornitza Stark Phenotypes for gene: CYP27A1 were changed from Cholestanol storage disease; Dystonia to Cerebrotendinous xanthomatosis, MIM# 213700; Cholestanol storage disease; Dystonia
Dystonia - complex v0.86 CYP27A1 Zornitza Stark Publications for gene: CYP27A1 were set to
Dystonia - complex v0.85 CYP27A1 Zornitza Stark edited their review of gene: CYP27A1: Changed rating: GREEN
Dystonia - complex v0.85 CYP27A1 Zornitza Stark reviewed gene: CYP27A1: Rating: ; Mode of pathogenicity: None; Publications: 19373932, 21531161, 25424010; Phenotypes: Cerebrotendinous xanthomatosis, MIM# 213700; Mode of inheritance: None
Dystonia - complex v0.85 CP Zornitza Stark Marked gene: CP as ready
Dystonia - complex v0.85 CP Zornitza Stark Gene: cp has been classified as Green List (High Evidence).
Dystonia - complex v0.85 CP Zornitza Stark Phenotypes for gene: CP were changed from Hemosiderosis, systemic, due to aceruloplasminemia 604290; Dystonia; Cerebellar ataxia 604290; Aceruloplasminemia; [Hypoceruloplasminemia, hereditary] 604290 to Aceruloplasminaemia, MIM#604290
Dystonia - complex v0.84 CP Zornitza Stark commented on gene: CP: Iron deposition in brain, specifically in basal ganglia, resulting in extrapyramidal movement disorders as part of the neurodegenerative phenotype.
Dystonia - complex v0.84 CLN3 Zornitza Stark Marked gene: CLN3 as ready
Dystonia - complex v0.84 CLN3 Zornitza Stark Gene: cln3 has been classified as Green List (High Evidence).
Dystonia - complex v0.84 CLN3 Zornitza Stark Classified gene: CLN3 as Green List (high evidence)
Dystonia - complex v0.84 CLN3 Zornitza Stark Gene: cln3 has been classified as Green List (High Evidence).
Dystonia - complex v0.83 CLN3 Zornitza Stark gene: CLN3 was added
gene: CLN3 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: CLN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLN3 were set to 19353721
Phenotypes for gene: CLN3 were set to Ceroid lipofuscinosis, neuronal, 3 204200
Review for gene: CLN3 was set to GREEN
Added comment: Movement disorders, including dystonia, are a feature of Batten disease.
Sources: Expert list
Dystonia - complex v0.82 CACNA1G Zornitza Stark changed review comment from: Variable spasticity, hypertonia, or dystonia of the limbs in addition to intellectual disability and ataxia.
Sources: Expert list; to: Four unrelated individuals reported with variable spasticity, hypertonia, or dystonia of the limbs in addition to intellectual disability and ataxia.
Sources: Expert list
Dystonia - complex v0.82 CACNA1G Zornitza Stark Marked gene: CACNA1G as ready
Dystonia - complex v0.82 CACNA1G Zornitza Stark Gene: cacna1g has been classified as Green List (High Evidence).
Dystonia - complex v0.82 CACNA1G Zornitza Stark Classified gene: CACNA1G as Green List (high evidence)
Dystonia - complex v0.82 CACNA1G Zornitza Stark Gene: cacna1g has been classified as Green List (High Evidence).
Dystonia - complex v0.81 CACNA1G Zornitza Stark gene: CACNA1G was added
gene: CACNA1G was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: CACNA1G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1G were set to 29878067
Phenotypes for gene: CACNA1G were set to Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits, MIM# 618087
Review for gene: CACNA1G was set to GREEN
Added comment: Variable spasticity, hypertonia, or dystonia of the limbs in addition to intellectual disability and ataxia.
Sources: Expert list
Dystonia - complex v0.80 C9orf72 Zornitza Stark Marked gene: C9orf72 as ready
Dystonia - complex v0.80 C9orf72 Zornitza Stark Gene: c9orf72 has been classified as Green List (High Evidence).
Dystonia - complex v0.80 C9orf72 Zornitza Stark Classified gene: C9orf72 as Green List (high evidence)
Dystonia - complex v0.80 C9orf72 Zornitza Stark Gene: c9orf72 has been classified as Green List (High Evidence).
Dystonia - complex v0.79 C9orf72 Zornitza Stark gene: C9orf72 was added
gene: C9orf72 was added to Dystonia - complex. Sources: Expert list
STR tags were added to gene: C9orf72.
Mode of inheritance for gene: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: C9orf72 were set to 26166205; 24363131; 26187722
Phenotypes for gene: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, MIM# 105550
Review for gene: C9orf72 was set to GREEN
Added comment: Dystonia is a well described feature of this condition. Note condition is caused by heterozygous hexanucleotide repeat expansion (GGGGCC) in a noncoding region of the C9ORF72 gene.
Sources: Expert list
Dystonia - complex v0.78 AUH Zornitza Stark Marked gene: AUH as ready
Dystonia - complex v0.78 AUH Zornitza Stark Gene: auh has been classified as Green List (High Evidence).
Dystonia - complex v0.78 AUH Zornitza Stark reviewed gene: AUH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria, type I, MIM# 250950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.78 ARX Zornitza Stark Marked gene: ARX as ready
Dystonia - complex v0.78 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Dystonia - complex v0.78 ARX Zornitza Stark Publications for gene: ARX were set to
Dystonia - complex v0.77 ARX Zornitza Stark edited their review of gene: ARX: Changed publications: 11889467, 15200506
Dystonia - complex v0.77 ARX Zornitza Stark Mode of pathogenicity for gene: ARX was changed from to Other
Dystonia - complex v0.76 ARX Zornitza Stark Phenotypes for gene: ARX were changed from Early infantile epileptic encephalopathy; Dystonia to Partington syndrome, MIM# 309510; Dystonia
Dystonia - complex v0.75 ARX Zornitza Stark reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Partington syndrome, MIM# 309510; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dystonia - complex v0.75 TIMM8A Zornitza Stark Marked gene: TIMM8A as ready
Dystonia - complex v0.75 TIMM8A Zornitza Stark Gene: timm8a has been classified as Green List (High Evidence).
Dystonia - complex v0.75 TIMM8A Zornitza Stark Phenotypes for gene: TIMM8A were changed from Deafness-Dystonia-Optic Neuronopathy Syndrome to Deafness-Dystonia-Optic Neuronopathy Syndrome; Mohr-Tranebjaerg syndrome, MIM# 304700
Dystonia - complex v0.74 TIMM8A Zornitza Stark Publications for gene: TIMM8A were set to
Dystonia - complex v0.73 TIMM8A Zornitza Stark Mode of inheritance for gene: TIMM8A was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dystonia - complex v0.72 TIMM8A Zornitza Stark reviewed gene: TIMM8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11803487, 11405816, 32820032; Phenotypes: Mohr-Tranebjaerg syndrome, MIM# 304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Dystonia - complex v0.72 GRIN1 Zornitza Stark Marked gene: GRIN1 as ready
Dystonia - complex v0.72 GRIN1 Zornitza Stark Gene: grin1 has been classified as Green List (High Evidence).
Dystonia - complex v0.72 GRIN1 Zornitza Stark Classified gene: GRIN1 as Green List (high evidence)
Dystonia - complex v0.72 GRIN1 Zornitza Stark Gene: grin1 has been classified as Green List (High Evidence).
Dystonia - complex v0.71 GRIN1 Zornitza Stark gene: GRIN1 was added
gene: GRIN1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: GRIN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GRIN1 were set to 29365063; 27164704; 27164704; 28051072
Phenotypes for gene: GRIN1 were set to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820
Review for gene: GRIN1 was set to GREEN
Added comment: Over 20 individuals reported with de novo missense variants in GRIN1 and severe neurodevelopmental phenotype, comprising ID, seizures, and a movement disorder, in particular dystonia. Two families reported with bi-allelic variants: different mechanism postulated (LOF vs affecting channel functioning or hypomorphic alleles), parents were carriers and unaffected. Movement disorder, in particular dystonia also reported in bi-allelic cases.
Sources: Expert list
Dystonia - complex v0.70 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Dystonia - complex v0.70 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Dystonia - complex v0.70 IRF2BPL Zornitza Stark Classified gene: IRF2BPL as Green List (high evidence)
Dystonia - complex v0.70 IRF2BPL Zornitza Stark Gene: irf2bpl has been classified as Green List (High Evidence).
Dystonia - complex v0.69 IRF2BPL Elena Savva gene: IRF2BPL was added
gene: IRF2BPL was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRF2BPL were set to PMID: 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088
Review for gene: IRF2BPL was set to GREEN
Added comment: PMID: 30057031 - 7 patients with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported.

PMID: 30166628 - 11 patients with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients.
Sources: Literature
Dystonia - complex v0.69 SQSTM1 Zornitza Stark Marked gene: SQSTM1 as ready
Dystonia - complex v0.69 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Green List (High Evidence).
Dystonia - complex v0.69 SQSTM1 Zornitza Stark Classified gene: SQSTM1 as Green List (high evidence)
Dystonia - complex v0.69 SQSTM1 Zornitza Stark Gene: sqstm1 has been classified as Green List (High Evidence).
Dystonia - complex v0.68 SQSTM1 Elena Savva gene: SQSTM1 was added
gene: SQSTM1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SQSTM1 were set to PMID: 27545679
Phenotypes for gene: SQSTM1 were set to Myopathy, distal, with rimmed vacuoles 617158
Review for gene: SQSTM1 was set to GREEN
Added comment: PMID: 27545679 - 9 patients (4 families) with childhood/adolescent onset neurodegeneration syndrome. 7/9 patients presented with dystonia. None noted to have myopathy.
Sources: Literature
Dystonia - complex v0.68 UBTF Bryony Thompson Marked gene: UBTF as ready
Dystonia - complex v0.68 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Dystonia - complex v0.68 UBTF Bryony Thompson Classified gene: UBTF as Green List (high evidence)
Dystonia - complex v0.68 UBTF Bryony Thompson Gene: ubtf has been classified as Green List (High Evidence).
Dystonia - complex v0.67 UBTF Bryony Thompson gene: UBTF was added
gene: UBTF was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBTF were set to 28777933; 29300972
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672
Mode of pathogenicity for gene: UBTF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: UBTF was set to GREEN
Added comment: 7 out of 11 unrelated cases with a recurrent de novo gain of function missense variant (p.Glu210Lys) have dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.66 FITM2 Bryony Thompson changed review comment from: Three unrelated cases with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list; to: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Dystonia - complex v0.66 FITM2 Bryony Thompson Marked gene: FITM2 as ready
Dystonia - complex v0.66 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Dystonia - complex v0.66 FITM2 Bryony Thompson Classified gene: FITM2 as Green List (high evidence)
Dystonia - complex v0.66 FITM2 Bryony Thompson Gene: fitm2 has been classified as Green List (High Evidence).
Dystonia - complex v0.65 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: Three unrelated cases with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Dystonia - complex v0.64 GSX2 Zornitza Stark Marked gene: GSX2 as ready
Dystonia - complex v0.64 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.64 GSX2 Zornitza Stark Classified gene: GSX2 as Amber List (moderate evidence)
Dystonia - complex v0.64 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.63 GSX2 Zornitza Stark gene: GSX2 was added
gene: GSX2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: GSX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSX2 were set to 31412107
Phenotypes for gene: GSX2 were set to Diencephalic-mesencephalic junction dysplasia syndrome 2 618646; Intellectual disability; Dystonia; Spastic tetra paresis
Review for gene: GSX2 was set to AMBER
Added comment: Two unrelated families, some functional data.
Sources: Literature
Dystonia - complex v0.62 SLC18A2 Zornitza Stark Marked gene: SLC18A2 as ready
Dystonia - complex v0.62 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.62 SLC18A2 Zornitza Stark Classified gene: SLC18A2 as Green List (high evidence)
Dystonia - complex v0.62 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Dystonia - complex v0.61 SLC18A2 Zornitza Stark gene: SLC18A2 was added
gene: SLC18A2 was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A2 were set to 23363473; 31240161; 26497564
Phenotypes for gene: SLC18A2 were set to Parkinsonism-dystonia, infantile, 2, MIM# 618049
Review for gene: SLC18A2 was set to GREEN
Added comment: At least three unrelated families reported, potential treatment implications. Associated with intellectual disability and epilepsy as well as prominent movement disorder.
Sources: Expert Review
Dystonia - complex v0.60 MECR Zornitza Stark Marked gene: MECR as ready
Dystonia - complex v0.60 MECR Zornitza Stark Gene: mecr has been classified as Green List (High Evidence).
Dystonia - complex v0.60 MECR Zornitza Stark Phenotypes for gene: MECR were changed from Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM#617282
Dystonia - complex v0.59 MECR Zornitza Stark Classified gene: MECR as Green List (high evidence)
Dystonia - complex v0.59 MECR Zornitza Stark Gene: mecr has been classified as Green List (High Evidence).
Dystonia - complex v0.58 ACTB Bryony Thompson reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: 25255767, 31970217, 28487785, 28849312, 29788902; Phenotypes: Dystonia, juvenile-onset MIM#607371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.58 MECR Elena Savva gene: MECR was added
gene: MECR was added to Dystonia - complex. Sources: Expert Review
Mode of inheritance for gene: MECR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MECR were set to PMID: 27817865; 31137067
Phenotypes for gene: MECR were set to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities
Review for gene: MECR was set to GREEN
Added comment: PMID: 27817865 - 4/5 families w/ bilallelic variants reported w/ dystonia with variable features

PMID: 31137067 - 1 patient w/ chet missense/PTCs and dystonia with variable features
Sources: Expert Review
Dystonia - complex v0.58 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Dystonia - complex v0.57 XK Bryony Thompson Marked gene: XK as ready
Dystonia - complex v0.57 XK Bryony Thompson Gene: xk has been classified as Green List (High Evidence).
Dystonia - complex v0.57 XK Bryony Thompson Classified gene: XK as Green List (high evidence)
Dystonia - complex v0.57 XK Bryony Thompson Gene: xk has been classified as Green List (High Evidence).
Dystonia - complex v0.56 XK Bryony Thompson gene: XK was added
gene: XK was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: XK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: XK were set to 11761473
Phenotypes for gene: XK were set to McLeod syndrome with or without chronic granulomatous disease MIM#300842
Review for gene: XK was set to GREEN
Added comment: 5 out of 13 cases had dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.55 VPS37A Bryony Thompson gene: VPS37A was added
gene: VPS37A was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: VPS37A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS37A were set to 22717650
Phenotypes for gene: VPS37A were set to Spastic paraplegia 53, autosomal recessive MIM#614898
Review for gene: VPS37A was set to RED
Added comment: Single consanguineous Arab Moslem kindred with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.54 UNC80 Bryony Thompson gene: UNC80 was added
gene: UNC80 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: UNC80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC80 were set to 26545877
Phenotypes for gene: UNC80 were set to hypotonia; severe intellectual disability; dyskinesia; dysmorphism
Review for gene: UNC80 was set to RED
Added comment: Two consanguineous Bedouin Israeli families homozygous for the same variantc.151C>T, p.(R51*) with dystonia as a feature of the condition. No other reported evidence for dystonia in the context of this condition.
Sources: Expert list
Dystonia - complex v0.53 TREX1 Bryony Thompson Marked gene: TREX1 as ready
Dystonia - complex v0.53 TREX1 Bryony Thompson Gene: trex1 has been classified as Green List (High Evidence).
Dystonia - complex v0.53 TREX1 Bryony Thompson Classified gene: TREX1 as Green List (high evidence)
Dystonia - complex v0.53 TREX1 Bryony Thompson Gene: trex1 has been classified as Green List (High Evidence).
Dystonia - complex v0.52 TREX1 Bryony Thompson gene: TREX1 was added
gene: TREX1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TREX1 were set to 20131292
Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive MIM#225750
Review for gene: TREX1 was set to GREEN
Added comment: 7 unrelated cases with dystonia as a feature of the condition, 6 biallelic and 1 de novo.
Sources: Expert list
Dystonia - complex v0.51 TOR1AIP1 Bryony Thompson reviewed gene: TOR1AIP1: Rating: RED; Mode of pathogenicity: None; Publications: 25425325; Phenotypes: Dystonia, Cerebellar Atrophy, Cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dystonia - complex v0.51 SYT1 Bryony Thompson Classified gene: SYT1 as Green List (high evidence)
Dystonia - complex v0.51 SYT1 Bryony Thompson Gene: syt1 has been classified as Green List (High Evidence).
Dystonia - complex v0.50 SYT1 Bryony Thompson gene: SYT1 was added
gene: SYT1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: SYT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYT1 were set to 30107533
Phenotypes for gene: SYT1 were set to Baker-Gordon syndrome MIM#618218
Review for gene: SYT1 was set to GREEN
Added comment: 4 out of 11 cases with a de novo variant had dystonia as a feature of the phenotype.
Sources: Expert list
Dystonia - complex v0.49 SUOX Bryony Thompson Classified gene: SUOX as Green List (high evidence)
Dystonia - complex v0.49 SUOX Bryony Thompson Gene: suox has been classified as Green List (High Evidence).
Dystonia - complex v0.48 SUOX Bryony Thompson gene: SUOX was added
gene: SUOX was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUOX were set to 9600976; 28933809; 16140720
Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency MIM#272300
Review for gene: SUOX was set to GREEN
Added comment: Dystonia is a feature of late-onset isolated sulfite oxidase deficiency. At least 6 cases reported with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.47 SNORD118 Bryony Thompson Classified gene: SNORD118 as Green List (high evidence)
Dystonia - complex v0.47 SNORD118 Bryony Thompson Gene: snord118 has been classified as Green List (High Evidence).
Dystonia - complex v0.46 SNORD118 Bryony Thompson gene: SNORD118 was added
gene: SNORD118 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: SNORD118 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNORD118 were set to 27571260
Phenotypes for gene: SNORD118 were set to Leukoencephalopathy, brain calcifications, and cysts MIM#614561
Review for gene: SNORD118 was set to GREEN
Added comment: At least 6 cases/families reported with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.45 SAMHD1 Bryony Thompson Classified gene: SAMHD1 as Amber List (moderate evidence)
Dystonia - complex v0.45 SAMHD1 Bryony Thompson Gene: samhd1 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.44 SAMHD1 Bryony Thompson gene: SAMHD1 was added
gene: SAMHD1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to 20131292
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5 MIM#612952
Review for gene: SAMHD1 was set to AMBER
Added comment: Two unrelated cases reported with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.43 RNASEH2C Bryony Thompson Classified gene: RNASEH2C as Green List (high evidence)
Dystonia - complex v0.43 RNASEH2C Bryony Thompson Gene: rnaseh2c has been classified as Green List (High Evidence).
Dystonia - complex v0.42 RNASEH2C Bryony Thompson gene: RNASEH2C was added
gene: RNASEH2C was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2C were set to 20131292; 23322642
Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3 MIM#610329
Review for gene: RNASEH2C was set to GREEN
Added comment: Three unrelated cases with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.41 RNASEH2B Bryony Thompson Classified gene: RNASEH2B as Green List (high evidence)
Dystonia - complex v0.41 RNASEH2B Bryony Thompson Gene: rnaseh2b has been classified as Green List (High Evidence).
Dystonia - complex v0.40 RNASEH2B Bryony Thompson gene: RNASEH2B was added
gene: RNASEH2B was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2B were set to 20131292; 26860721
Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2 MIM#610181
Review for gene: RNASEH2B was set to GREEN
Added comment: 3 or 4 cases with biallelic variants (one of the publications in Spanish and unsure if both cases have dystonia) with dystonia as a feature of the condition. Two other cases with dystonia as a feature, but only a single heterozygous variant was identified.
Sources: Expert list
Dystonia - complex v0.39 RNASEH2A Bryony Thompson gene: RNASEH2A was added
gene: RNASEH2A was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2A were set to 20131292
Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4 MIM#610333
Review for gene: RNASEH2A was set to RED
Added comment: Single case reported with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.38 PLP1 Bryony Thompson gene: PLP1 was added
gene: PLP1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLP1 were set to 30046645; 19396823
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease MIM#312080
Review for gene: PLP1 was set to RED
Added comment: Dystonia has been reported as a feature of PMD in two cases/families. It does not appear to be a prominent feature of the condition.
Sources: Expert list
Dystonia - complex v0.37 PDHA1 Bryony Thompson Marked gene: PDHA1 as ready
Dystonia - complex v0.37 PDHA1 Bryony Thompson Gene: pdha1 has been classified as Green List (High Evidence).
Dystonia - complex v0.37 PDHA1 Bryony Thompson Classified gene: PDHA1 as Green List (high evidence)
Dystonia - complex v0.37 PDHA1 Bryony Thompson Gene: pdha1 has been classified as Green List (High Evidence).
Dystonia - complex v0.36 PDHA1 Bryony Thompson gene: PDHA1 was added
gene: PDHA1 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PDHA1 were set to 20002125
Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170
Review for gene: PDHA1 was set to GREEN
Added comment: At least four cases reported with dystonia as a feature of the condition.
Sources: Literature
Dystonia - complex v0.35 PDHX Bryony Thompson Classified gene: PDHX as Green List (high evidence)
Dystonia - complex v0.35 PDHX Bryony Thompson Gene: pdhx has been classified as Green List (High Evidence).
Dystonia - complex v0.34 PDHX Bryony Thompson gene: PDHX was added
gene: PDHX was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: PDHX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHX were set to 20002125; 16566017; 17152059
Phenotypes for gene: PDHX were set to Lacticacidemia due to PDX1 deficiency MIM#245349
Review for gene: PDHX was set to GREEN
Added comment: At least four cases reported with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.33 NKX2-1 Bryony Thompson Marked gene: NKX2-1 as ready
Dystonia - complex v0.33 NKX2-1 Bryony Thompson Gene: nkx2-1 has been classified as Green List (High Evidence).
Dystonia - complex v0.33 NKX2-1 Bryony Thompson Classified gene: NKX2-1 as Green List (high evidence)
Dystonia - complex v0.33 NKX2-1 Bryony Thompson Gene: nkx2-1 has been classified as Green List (High Evidence).
Dystonia - complex v0.32 NKX2-1 Bryony Thompson gene: NKX2-1 was added
gene: NKX2-1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-1 were set to 24714694; 30186310
Phenotypes for gene: NKX2-1 were set to Chorea, hereditary benign MIM#118700; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978
Review for gene: NKX2-1 was set to GREEN
Added comment: At least 7 cases with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.31 MPV17 Bryony Thompson gene: MPV17 was added
gene: MPV17 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: MPV17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPV17 were set to 29282788
Phenotypes for gene: MPV17 were set to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) MIM#256810
Review for gene: MPV17 was set to RED
Added comment: Dystonia is not a prominent feature of the condition. It has been reported in 4/91 (4%) of cases. There are other features that are more prominent.
Sources: Expert list
Dystonia - complex v0.30 MMADHC Bryony Thompson gene: MMADHC was added
gene: MMADHC was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: MMADHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMADHC were set to 15292234; 18385497
Phenotypes for gene: MMADHC were set to Homocystinuria, cblD type, variant 1 MIM#277410
Review for gene: MMADHC was set to RED
Added comment: Single case reported with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.29 MAT1A Bryony Thompson gene: MAT1A was added
gene: MAT1A was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: MAT1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAT1A were set to 8770875
Phenotypes for gene: MAT1A were set to Methionine adenosyltransferase deficiency, autosomal recessive MIM#250850
Review for gene: MAT1A was set to RED
Added comment: Single case reported with dystonia a feature of the condition.
Sources: Expert list
Dystonia - complex v0.28 MARS2 Bryony Thompson Marked gene: MARS2 as ready
Dystonia - complex v0.28 MARS2 Bryony Thompson Gene: mars2 has been classified as Green List (High Evidence).
Dystonia - complex v0.28 MARS2 Bryony Thompson Classified gene: MARS2 as Green List (high evidence)
Dystonia - complex v0.28 MARS2 Bryony Thompson Added comment: Comment on list classification: Large duplications that are not detected by WES are the only reported cause of the form of spastic ataxia caused by this gene.
Dystonia - complex v0.28 MARS2 Bryony Thompson Gene: mars2 has been classified as Green List (High Evidence).
Dystonia - complex v0.27 MARS2 Bryony Thompson Tag SV/CNV tag was added to gene: MARS2.
Dystonia - complex v0.27 MARS2 Bryony Thompson gene: MARS2 was added
gene: MARS2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS2 were set to 16672289; 22448145
Phenotypes for gene: MARS2 were set to Spastic ataxia 3, autosomal recessive MIM#611390
Review for gene: MARS2 was set to GREEN
Added comment: 57% of 23 cases from 17 French-Canadian spastic ataxia families had dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.26 MAPT Bryony Thompson gene: MAPT was added
gene: MAPT was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: MAPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAPT were set to 17319286; 15883319
Phenotypes for gene: MAPT were set to Dementia, frontotemporal, with or without parkinsonism MIM#600274
Review for gene: MAPT was set to AMBER
Added comment: Dystonia has been reported in two cases. Cannot find evidence that dystonia is a prominent feature associated with MAPT variants.
Sources: Expert list
Dystonia - complex v0.25 L2HGDH Bryony Thompson Marked gene: L2HGDH as ready
Dystonia - complex v0.25 L2HGDH Bryony Thompson Gene: l2hgdh has been classified as Green List (High Evidence).
Dystonia - complex v0.25 L2HGDH Bryony Thompson Classified gene: L2HGDH as Green List (high evidence)
Dystonia - complex v0.25 L2HGDH Bryony Thompson Gene: l2hgdh has been classified as Green List (High Evidence).
Dystonia - complex v0.24 L2HGDH Bryony Thompson gene: L2HGDH was added
gene: L2HGDH was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: L2HGDH were set to 24753671; 18780161; 15824270; 10399870
Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria MIM#236792
Review for gene: L2HGDH was set to GREEN
Added comment: Four families with dystonia as a feature of the condition.
Sources: Expert list
Dystonia - complex v0.23 KCNQ2 Bryony Thompson gene: KCNQ2 was added
gene: KCNQ2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: KCNQ2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNQ2 were set to 12742592
Phenotypes for gene: KCNQ2 were set to Epileptic encephalopathy, early infantile, 7 MIM#613720
Review for gene: KCNQ2 was set to RED
Added comment: Cannot find evidence that dystonia is a prominent feature of the condition. Single case reported with dystonic features from 2003
Sources: Expert list
Dystonia - complex v0.22 HACE1 Bryony Thompson Marked gene: HACE1 as ready
Dystonia - complex v0.22 HACE1 Bryony Thompson Gene: hace1 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.22 HACE1 Bryony Thompson Classified gene: HACE1 as Amber List (moderate evidence)
Dystonia - complex v0.22 HACE1 Bryony Thompson Gene: hace1 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.21 HACE1 Bryony Thompson gene: HACE1 was added
gene: HACE1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: HACE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HACE1 were set to 26424145; 26437029
Phenotypes for gene: HACE1 were set to Spastic paraplegia and psychomotor retardation with or without seizures MIM#616756
Review for gene: HACE1 was set to AMBER
Added comment: Two families where 1/5 and 1/3 affected cases has dystonic movements as part of their phenotype, respectively (PMID: 26424145). Members of two out of four families have spasticity/dystonia features, with no further differentiation supplied (PMID: 26437029).
Sources: Expert list
Dystonia - complex v0.20 GAMT Bryony Thompson gene: GAMT was added
gene: GAMT was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: GAMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAMT were set to 19027335
Phenotypes for gene: GAMT were set to Cerebral creatine deficiency syndrome 2 MIM#612736
Review for gene: GAMT was set to RED
Added comment: Dystonia is not a prominent feature of the condition. A single case has been reported with dystonia as part of the phenotype.
Sources: Expert list
Dystonia - complex v0.19 FBXL4 Bryony Thompson Marked gene: FBXL4 as ready
Dystonia - complex v0.19 FBXL4 Bryony Thompson Gene: fbxl4 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.19 FBXL4 Bryony Thompson Classified gene: FBXL4 as Amber List (moderate evidence)
Dystonia - complex v0.19 FBXL4 Bryony Thompson Gene: fbxl4 has been classified as Amber List (Moderate Evidence).
Dystonia - complex v0.18 FBXL4 Bryony Thompson changed review comment from: Cannot find evidence that dystonia is a prominent feature of the condition.
Sources: Expert list; to: Dystonia is a feature of the phenotype in three out of nine cases with biallelic variants.
Sources: Expert list
Dystonia - complex v0.18 FBXL4 Bryony Thompson edited their review of gene: FBXL4: Changed rating: AMBER
Dystonia - complex v0.18 FBXL4 Bryony Thompson gene: FBXL4 was added
gene: FBXL4 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: FBXL4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FBXL4 were set to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471
Review for gene: FBXL4 was set to RED
Added comment: Cannot find evidence that dystonia is a prominent feature of the condition.
Sources: Expert list
Dystonia - complex v0.17 EARS2 Bryony Thompson gene: EARS2 was added
gene: EARS2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EARS2 were set to 22492562
Phenotypes for gene: EARS2 were set to Combined oxidative phosphorylation deficiency 12 MIM#614924
Review for gene: EARS2 was set to RED
Added comment: Dystonia does not appear to be a prominent feature of the condition.
Sources: Expert list
Dystonia - complex v0.16 DCTN1 Bryony Thompson Marked gene: DCTN1 as ready
Dystonia - complex v0.16 DCTN1 Bryony Thompson Gene: dctn1 has been classified as Red List (Low Evidence).
Dystonia - complex v0.16 DCTN1 Bryony Thompson gene: DCTN1 was added
gene: DCTN1 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: DCTN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCTN1 were set to 24343258
Phenotypes for gene: DCTN1 were set to Perry syndrome MIM#168605
Review for gene: DCTN1 was set to RED
Added comment: Dystonia is reported in two out of eight cases in a single family.
Sources: Expert list
Dystonia - complex v0.15 CHMP2B Bryony Thompson reviewed gene: CHMP2B: Rating: RED; Mode of pathogenicity: None; Publications: 12451202; Phenotypes: Dementia, familial, nonspecific MIM#600795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - complex v0.15 CACNA1A Bryony Thompson Classified gene: CACNA1A as Green List (high evidence)
Dystonia - complex v0.15 CACNA1A Bryony Thompson Gene: cacna1a has been classified as Green List (High Evidence).
Dystonia - complex v0.14 CACNA1A Bryony Thompson gene: CACNA1A was added
gene: CACNA1A was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to 25468264; 23441182; 19232643; 18758887; 11344116
Phenotypes for gene: CACNA1A were set to Episodic ataxia, type 2 MIM#108500; Spinocerebellar ataxia 6 MIM#183086
Review for gene: CACNA1A was set to GREEN
Added comment: At least four families where dystonia is a feature of the condition (complex dystonia phenotype), and knockout mouse model also has dystonia as a feature of the phenotype.
Sources: Expert list
Dystonia - complex v0.13 AFG3L2 Bryony Thompson gene: AFG3L2 was added
gene: AFG3L2 was added to Dystonia - complex. Sources: Expert list
Mode of inheritance for gene: AFG3L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AFG3L2 were set to 22964162; 16541453
Phenotypes for gene: AFG3L2 were set to Spastic ataxia 5, autosomal recessive MIM#614487
Review for gene: AFG3L2 was set to RED
Added comment: Dystonia is not a prominent feature of this condition. There is a single family reported with complex dystonia. Dystonia was previously observed in a family whose affected members carried an 18p chromosomal deletion that included AFG3L2.
Sources: Expert list
Dystonia - complex v0.12 Bryony Thompson Panel name changed from Dystonia - complex_RMH to Dystonia - complex
Panel types changed to Royal Melbourne Hospital; Rare Disease
Dystonia - complex v0.10 GRN Bryony Thompson Marked gene: GRN as ready
Dystonia - complex v0.10 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Dystonia - complex v0.10 GRN Bryony Thompson Classified gene: GRN as Green List (high evidence)
Dystonia - complex v0.10 GRN Bryony Thompson Gene: grn has been classified as Green List (High Evidence).
Dystonia - complex v0.9 GRN Bryony Thompson gene: GRN was added
gene: GRN was added to Dystonia - complex_RMH. Sources: Expert list
Mode of inheritance for gene: GRN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GRN were set to Frontotemporal lobar degeneration with ubiquitin-positive inclusions, MIM#607485
Review for gene: GRN was set to GREEN
Added comment: Dystonia is a reported feature of the phenotype
Sources: Expert list
Dystonia - complex v0.8 GM2A Bryony Thompson Marked gene: GM2A as ready
Dystonia - complex v0.8 GM2A Bryony Thompson Gene: gm2a has been classified as Green List (High Evidence).
Dystonia - complex v0.8 GM2A Bryony Thompson Classified gene: GM2A as Green List (high evidence)
Dystonia - complex v0.8 GM2A Bryony Thompson Gene: gm2a has been classified as Green List (High Evidence).
Dystonia - complex v0.7 GM2A Bryony Thompson gene: GM2A was added
gene: GM2A was added to Dystonia - complex_RMH. Sources: Expert list
Mode of inheritance for gene: GM2A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GM2A were set to GM2-gangliosidosis, AB variant, MIM#272750
Review for gene: GM2A was set to GREEN
Added comment: Dystonia is a feature of the phenotype
Sources: Expert list
Dystonia - complex v0.6 GALT Bryony Thompson Marked gene: GALT as ready
Dystonia - complex v0.6 GALT Bryony Thompson Gene: galt has been classified as Green List (High Evidence).
Dystonia - complex v0.6 GALT Bryony Thompson Classified gene: GALT as Green List (high evidence)
Dystonia - complex v0.6 GALT Bryony Thompson Gene: galt has been classified as Green List (High Evidence).
Dystonia - complex v0.5 GALT Bryony Thompson gene: GALT was added
gene: GALT was added to Dystonia - complex_RMH. Sources: Expert list
Mode of inheritance for gene: GALT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALT were set to 30718057
Phenotypes for gene: GALT were set to Galactosemia, MIM#230400
Review for gene: GALT was set to GREEN
Added comment: Dystonia can be a feature of the phenotype (PMID: 30718057).
Sources: Expert list
Dystonia - complex v0.4 FUCA1 Bryony Thompson Marked gene: FUCA1 as ready
Dystonia - complex v0.4 FUCA1 Bryony Thompson Gene: fuca1 has been classified as Green List (High Evidence).
Dystonia - complex v0.4 FUCA1 Bryony Thompson Classified gene: FUCA1 as Green List (high evidence)
Dystonia - complex v0.4 FUCA1 Bryony Thompson Gene: fuca1 has been classified as Green List (High Evidence).
Dystonia - complex v0.3 FUCA1 Bryony Thompson gene: FUCA1 was added
gene: FUCA1 was added to Dystonia - complex_RMH. Sources: Expert list
Mode of inheritance for gene: FUCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUCA1 were set to 31064022
Phenotypes for gene: FUCA1 were set to Fucosidosis, MIM#230000
Review for gene: FUCA1 was set to GREEN
Added comment: Dystonia can be a feature of the phenotype. Dystonia was present in 9/75 Fucosidosis cases in a literature review (PMID: 31064022).
Sources: Expert list
Dystonia - complex v0.2 ARSA Bryony Thompson Marked gene: ARSA as ready
Dystonia - complex v0.2 ARSA Bryony Thompson Gene: arsa has been classified as Green List (High Evidence).
Dystonia - complex v0.2 ARSA Bryony Thompson Classified gene: ARSA as Green List (high evidence)
Dystonia - complex v0.2 ARSA Bryony Thompson Gene: arsa has been classified as Green List (High Evidence).
Dystonia - complex v0.1 ARSA Bryony Thompson gene: ARSA was added
gene: ARSA was added to Dystonia - complex_RMH. Sources: Expert list
Mode of inheritance for gene: ARSA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARSA were set to Metachromatic leukodystrophy, MIM#250100
Review for gene: ARSA was set to GREEN
Added comment: Dystonia is a feature of the phenotype
Sources: Expert list
Dystonia - complex v0.0 YY1 Bryony Thompson gene: YY1 was added
gene: YY1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: YY1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: YY1 were set to Gabriele-de Vries syndrome 617557
Dystonia - complex v0.0 WDR73 Bryony Thompson gene: WDR73 was added
gene: WDR73 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: WDR73 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR73 were set to Galloway-Mowat syndrome 1, 251300
Dystonia - complex v0.0 WDR45 Bryony Thompson gene: WDR45 was added
gene: WDR45 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: WDR45 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: WDR45 were set to Neurodegeneration with brain iron accumulation 5 300894; beta-propeller protein-associated neurodegeneration; Dystonia
Dystonia - complex v0.0 VPS13A Bryony Thompson gene: VPS13A was added
gene: VPS13A was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: VPS13A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13A were set to complex parkinsonism; Choreoacanthocytosis 200150
Dystonia - complex v0.0 VAC14 Bryony Thompson gene: VAC14 was added
gene: VAC14 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: VAC14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VAC14 were set to Striatonigral degeneration, childhood-onset 617054
Dystonia - complex v0.0 TPK1 Bryony Thompson gene: TPK1 was added
gene: TPK1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type); Dystonia
Dystonia - complex v0.0 TOR1AIP1 Bryony Thompson gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Red
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 25425325
Phenotypes for gene: TOR1AIP1 were set to Dystonia, cerebellar atrophy, and cardiomyopathy
Dystonia - complex v0.0 TIMM8A Bryony Thompson gene: TIMM8A was added
gene: TIMM8A was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: TIMM8A was set to
Phenotypes for gene: TIMM8A were set to Deafness-Dystonia-Optic Neuronopathy Syndrome
Dystonia - complex v0.0 SYNJ1 Bryony Thompson gene: SYNJ1 was added
gene: SYNJ1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SYNJ1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SYNJ1 were set to juvenile Parkinsonism; Parkinson disease 20, early-onset
Dystonia - complex v0.0 SUCLA2 Bryony Thompson gene: SUCLA2 was added
gene: SUCLA2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SUCLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SUCLA2 were set to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria); Dystonia
Dystonia - complex v0.0 SLC6A3 Bryony Thompson gene: SLC6A3 was added
gene: SLC6A3 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SLC6A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC6A3 were set to Dopamine transporter deficiency; Parkinsonism-dystonia, infantile, 613135
Dystonia - complex v0.0 SLC39A14 Bryony Thompson gene: SLC39A14 was added
gene: SLC39A14 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SLC39A14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC39A14 were set to Hypermanganesemia with dystonia 2 617013
Dystonia - complex v0.0 SLC30A10 Bryony Thompson gene: SLC30A10 was added
gene: SLC30A10 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC30A10 were set to Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease; Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280
Dystonia - complex v0.0 SLC20A2 Bryony Thompson gene: SLC20A2 was added
gene: SLC20A2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SLC20A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLC20A2 were set to Basal ganglia calcification, idiopathic, 1 213600; Dystonia
Dystonia - complex v0.0 SLC19A3 Bryony Thompson gene: SLC19A3 was added
gene: SLC19A3 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) 607483; Dystonia
Dystonia - complex v0.0 SERAC1 Bryony Thompson gene: SERAC1 was added
gene: SERAC1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SERAC1 were set to 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; Lesions in the basal ganglia
Dystonia - complex v0.0 QDPR Bryony Thompson gene: QDPR was added
gene: QDPR was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: QDPR were set to Hyperphenylalaninemia, BH4-deficient, C, 261630; Dihydropteridine reductase deficiency; Dystonia
Dystonia - complex v0.0 PTS Bryony Thompson gene: PTS was added
gene: PTS was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PTS were set to Hyperphenylalaninemia, BH4-deficient, A, 261640; 6-Pyruvoyltetrahydropterin Synthase Deficiency; Dystonia
Dystonia - complex v0.0 PSEN1 Bryony Thompson gene: PSEN1 was added
gene: PSEN1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PSEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PSEN1 were set to 28664294; 12810495; 15159497; 29316780
Phenotypes for gene: PSEN1 were set to Frontotemporal dementia; Dystonia
Dystonia - complex v0.0 PRKN Bryony Thompson gene: PRKN was added
gene: PRKN was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PRKN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PRKN were set to juvenile parkinsonism/dystonia; Parkinson disease, juvenile, type 2; Dystonia
Dystonia - complex v0.0 PLA2G6 Bryony Thompson gene: PLA2G6 was added
gene: PLA2G6 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLA2G6 were set to Parkinson disease 14, autosomal recessive 612953; PLA2G6-associated neurodegeneration; Neurodegeneration with brain iron accumulation 2B 610217; Infantile neuroaxonal dystrophy 1 256600
Dystonia - complex v0.0 PINK1 Bryony Thompson gene: PINK1 was added
gene: PINK1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PINK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PINK1 were set to Parkinson disease 6, early onset; Dystonia
Dystonia - complex v0.0 PDGFRB Bryony Thompson gene: PDGFRB was added
gene: PDGFRB was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PDGFRB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PDGFRB were set to Dystonia; Basal ganglia calcification, idiopathic, 4 615007
Dystonia - complex v0.0 PDGFB Bryony Thompson gene: PDGFB was added
gene: PDGFB was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PDGFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PDGFB were set to Basal ganglia calcification, idiopathic, 5 615483
Dystonia - complex v0.0 PANK2 Bryony Thompson gene: PANK2 was added
gene: PANK2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PANK2 were set to pantothenate kinase-associated neurodegeneration; Dystonia
Dystonia - complex v0.0 NPC2 Bryony Thompson gene: NPC2 was added
gene: NPC2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPC2 were set to Niemann-Pick disease type C2; Dystonia
Dystonia - complex v0.0 NPC1 Bryony Thompson gene: NPC1 was added
gene: NPC1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPC1 were set to Niemann-Pick disease type C1
Dystonia - complex v0.0 NKX6-2 Bryony Thompson gene: NKX6-2 was added
gene: NKX6-2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: NKX6-2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NKX6-2 were set to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 617560
Dystonia - complex v0.0 HTRA2 Bryony Thompson gene: HTRA2 was added
gene: HTRA2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: HTRA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HTRA2 were set to 3-methylglutaconic aciduria, type VIII 617248
Dystonia - complex v0.0 HPRT1 Bryony Thompson gene: HPRT1 was added
gene: HPRT1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: HPRT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: HPRT1 were set to Lesch-Nyhan syndrome; Dystonia
Dystonia - complex v0.0 GNB1 Bryony Thompson gene: GNB1 was added
gene: GNB1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GNB1 were set to 30194818
Phenotypes for gene: GNB1 were set to Mental retardation, autosomal dominant 42; Myoclonus dystonia
Dystonia - complex v0.0 GNAO1 Bryony Thompson gene: GNAO1 was added
gene: GNAO1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GNAO1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GNAO1 were set to Neurodevelopmental disorder with involuntary movements, 617493
Dystonia - complex v0.0 GLB1 Bryony Thompson gene: GLB1 was added
gene: GLB1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GLB1 were set to Infantile GM1 gangliosidosis
Dystonia - complex v0.0 GCDH Bryony Thompson gene: GCDH was added
gene: GCDH was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GCDH were set to Glutaric aciduria, type 1; Dystonia
Dystonia - complex v0.0 FTL Bryony Thompson gene: FTL was added
gene: FTL was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FTL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FTL were set to Neurodegeneration with brain iron accumulation 3 606159
Dystonia - complex v0.0 FOXG1 Bryony Thompson gene: FOXG1 was added
gene: FOXG1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FOXG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FOXG1 were set to Rett syndrome, congenital variant; Dystonia
Dystonia - complex v0.0 FBXO7 Bryony Thompson gene: FBXO7 was added
gene: FBXO7 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FBXO7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FBXO7 were set to juvenile parkinsonism; Dystonia
Dystonia - complex v0.0 FA2H Bryony Thompson gene: FA2H was added
gene: FA2H was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FA2H were set to Dystonia; Spastic paraplegia 35, autosomal recessive 612319; fatty acid hydroxylase-associated neurodegeneration
Dystonia - complex v0.0 DNAJC12 Bryony Thompson gene: DNAJC12 was added
gene: DNAJC12 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: DNAJC12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAJC12 were set to Hyperphenylalaninemia, mild, non-BH4-deficient, 617384
Dystonia - complex v0.0 DLAT Bryony Thompson gene: DLAT was added
gene: DLAT was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: DLAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DLAT were set to Pyruvate dehydrogenase E2 deficiency 245348; Dystonia
Dystonia - complex v0.0 DDC Bryony Thompson gene: DDC was added
gene: DDC was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: DDC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DDC were set to Aromatic L-amino acid decarboxylase deficiency, 608643; Dystonia
Dystonia - complex v0.0 DCAF17 Bryony Thompson gene: DCAF17 was added
gene: DCAF17 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: DCAF17 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF17 were set to Woodhouse-Sakati syndrome; Dystonia
Dystonia - complex v0.0 CYP27A1 Bryony Thompson gene: CYP27A1 was added
gene: CYP27A1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP27A1 were set to Cholestanol storage disease; Dystonia
Dystonia - complex v0.0 CP Bryony Thompson gene: CP was added
gene: CP was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: CP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CP were set to Hemosiderosis, systemic, due to aceruloplasminemia 604290; Dystonia; Cerebellar ataxia 604290; Aceruloplasminemia; [Hypoceruloplasminemia, hereditary] 604290
Dystonia - complex v0.0 COASY Bryony Thompson gene: COASY was added
gene: COASY was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COASY were set to COASY protein-associated neurodegeneration; Neurodegeneration with brain iron accumulation 6 615643
Dystonia - complex v0.0 CHMP2B Bryony Thompson gene: CHMP2B was added
gene: CHMP2B was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Red
Mode of inheritance for gene: CHMP2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CHMP2B were set to 20301378
Phenotypes for gene: CHMP2B were set to familial frontotemporal lobar degeneration (ALS17); Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Dystonia
Dystonia - complex v0.0 C19orf12 Bryony Thompson gene: C19orf12 was added
gene: C19orf12 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: C19orf12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: C19orf12 were set to mitochondrial membrane protein-associated neurodegeneration; neurodegeneration with brain iron accumulation-4; Dystonia
Dystonia - complex v0.0 BCAP31 Bryony Thompson gene: BCAP31 was added
gene: BCAP31 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: BCAP31 were set to Deafness, dystonia and cerebellar hypomyelination, 300475
Dystonia - complex v0.0 AUH Bryony Thompson gene: AUH was added
gene: AUH was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: AUH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AUH were set to 3-Methylglutaconic aciduria type 1; Dystonia
Dystonia - complex v0.0 ATP7B Bryony Thompson gene: ATP7B was added
gene: ATP7B was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP7B were set to Wilson disease 277900; Dystonia
Dystonia - complex v0.0 ATP13A2 Bryony Thompson gene: ATP13A2 was added
gene: ATP13A2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP13A2 were set to Parkinson disease; Kufor-Rakeb syndrome 606693; Dystonia
Dystonia - complex v0.0 ATM Bryony Thompson gene: ATM was added
gene: ATM was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATM were set to Ataxia telangiectasia; Dystonia
Dystonia - complex v0.0 ARX Bryony Thompson gene: ARX was added
gene: ARX was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ARX was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: ARX were set to Early infantile epileptic encephalopathy; Dystonia
Dystonia - complex v0.0 APTX Bryony Thompson gene: APTX was added
gene: APTX was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: APTX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: APTX were set to Ataxia-oculomotor apraxia type 1; Dystonia
Dystonia - complex v0.0 ADAR Bryony Thompson gene: ADAR was added
gene: ADAR was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ADAR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ADAR were set to dystonia; Aicardi-Goutieres syndrome 6, 615010
Dystonia - complex v0.0 ACTB Bryony Thompson gene: ACTB was added
gene: ACTB was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green
Mode of inheritance for gene: ACTB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACTB were set to 29788902; 28487785
Phenotypes for gene: ACTB were set to Baraitser-Winter syndrome 1, 243310; Dystonia, juvenile-onset, 607371
Dystonia - complex v0.0 Bryony Thompson Added panel Dystonia - complex_RMH