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Early-onset Parkinson disease v2.2 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson changed review comment from: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls).
The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase.
Sources: Literature; to: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls).
The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase.
The variant is reported as a novel reduced penetrance PD risk factor. The 95% CI for the OR estimate are very wide. A confirmatory study is required for this variant.
Sources: Literature
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson edited their review of gene: RAB32: Changed rating: RED
Early-onset Parkinson disease v2.1 RAB32 Bryony Thompson gene: RAB32 was added
gene: RAB32 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: RAB32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB32 were set to 38614108
Phenotypes for gene: RAB32 were set to Parkinson disease MONDO:0005180
Mode of pathogenicity for gene: RAB32 was set to Other
Review for gene: RAB32 was set to AMBER
Added comment: A single variant in RAB32 - c.213C>G p.(Ser71Arg) with a significant association with PD (odds ratio [OR] 13.17, 95% CI 2.15-87.23; p=0.0055, 6,043 PD cases and 62,549 controls).
The variant cosegregated with autosomal dominant PD in 3 families (9 affected individuals), with incomplete penetrance. In vitro studies demonstrate that RAB32 Ser71Arg activates LRRK2 kinase.
Sources: Literature
Early-onset Parkinson disease v0.345 WDR45 Bryony Thompson Mode of inheritance for gene: WDR45 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.344 VPS13A Bryony Thompson Phenotypes for gene: VPS13A were changed from to chorea-acanthocytosis MONDO:0008695
Early-onset Parkinson disease v0.340 TUBB4A Bryony Thompson Added comment: Comment on list classification: More suitable for the dystonia panel
Early-onset Parkinson disease v0.339 TH Bryony Thompson Marked gene: TH as ready
Early-onset Parkinson disease v0.339 TH Bryony Thompson Gene: th has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.339 TH Bryony Thompson Phenotypes for gene: TH were changed from to Tyrosine hydroxylase deficiency MONDO:0100064
Early-onset Parkinson disease v0.338 TH Bryony Thompson Publications for gene: TH were set to 20301334; 20301610
Early-onset Parkinson disease v0.337 TH Bryony Thompson Publications for gene: TH were set to
Early-onset Parkinson disease v0.336 TH Bryony Thompson Mode of inheritance for gene: TH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.330 SLC30A10 Bryony Thompson Phenotypes for gene: SLC30A10 were changed from to cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome MONDO:0013208
Early-onset Parkinson disease v0.314 ANG Bryony Thompson gene: ANG was added
gene: ANG was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ANG was set to Unknown
Publications for gene: ANG were set to 33875291; 25386690
Phenotypes for gene: ANG were set to Parkinson disease MONDO:0005180
Review for gene: ANG was set to RED
Added comment: Multiple large studies not finding an association with PD
Sources: Literature
Early-onset Parkinson disease v0.313 FUS Bryony Thompson changed review comment from: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature; to: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. One of these (Pro431Leu) was also reported in an Italian family. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature
Early-onset Parkinson disease v0.313 FUS Bryony Thompson edited their review of gene: FUS: Changed publications: 22863194, 23834483, 23825177, 38626532
Early-onset Parkinson disease v0.312 FUS Bryony Thompson gene: FUS was added
gene: FUS was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FUS were set to 22863194
Phenotypes for gene: FUS were set to tremor, hereditary essential, 4 MONDO:0013888
Review for gene: FUS was set to RED
Added comment: A single family reported p.Gln290* segregating (incomplete penetrance) with essential tremor, also two missense variants reported in 2 probands which are too common in gnomAD and have been classified as LB in ClinVar. A reported ET risk variant Met392Ile in a Chinese population - set 1 odds ratio = 4.72 [95% confidence interval = 1.90-11.71], p = 0.0037). Validation set 2 (joint analysis odds ratio = 3.92 [95% confidence interval = 1.57-9.82], p = 8.6 × 10(-4). This variant has been classified as LB in ClinVar.
Sources: Literature
Early-onset Parkinson disease v0.306 VCP Bryony Thompson gene: VCP was added
gene: VCP was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 38283104; 38145206
Phenotypes for gene: VCP were set to Inclusion body myopathy with Paget disease of bone and frontotemporal dementia MONDO:0000507
Mode of pathogenicity for gene: VCP was set to Other
Review for gene: VCP was set to GREEN
gene: VCP was marked as current diagnostic
Added comment: Parkinsonism is a rare feature of VCP-related multisystem proteinopathy, but has been reported in at least 15 individuals with VCP variants.
Sources: Literature
Early-onset Parkinson disease v0.302 LYST Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a feature of the condition
Early-onset Parkinson disease v0.295 LRRK2 Sangavi Sivagnanasundram reviewed gene: LRRK2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 1626954, https://search.clinicalgenome.org/CCID:005305; Phenotypes: Parkinson disease (MONDO:0005180); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.295 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from early-onset parkinsonism; intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Early-onset Parkinson disease v0.294 PTRHD1 Zornitza Stark reviewed gene: PTRHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Added comment: Comment on list classification: Parkinsonism can be a presenting feature of the condition
Early-onset Parkinson disease v0.291 FTL Bryony Thompson Added comment: Comment on list classification: Parkinsonism can be a presenting feature of the condition
Early-onset Parkinson disease v0.279 CSF1R Bryony Thompson Phenotypes for gene: CSF1R were changed from to leukoencephalopathy, diffuse hereditary, with spheroids 1 MONDO:0800027
Early-onset Parkinson disease v0.276 CSF1R Bryony Thompson Added comment: Comment on list classification: Parkinsonian signs can be a feature on the condition
Early-onset Parkinson disease v0.275 C19orf12 Bryony Thompson Phenotypes for gene: C19orf12 were changed from to neurodegeneration with brain iron accumulation 4 MONDO:0013674
Early-onset Parkinson disease v0.269 ATP1A3 Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a major feature of the condition
Early-onset Parkinson disease v0.264 WDR45 Kaitlyn Dianna Weldon reviewed gene: WDR45: Rating: GREEN; Mode of pathogenicity: None; Publications: 28211668; Phenotypes: neurodegeneration with brain iron accumulation 5 MONDO:0010476, X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.264 VPS13A Kaitlyn Dianna Weldon reviewed gene: VPS13A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301561, 37636221; Phenotypes: chorea-acanthocytosis MONDO:0008695; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.264 TUBB4A Kaitlyn Dianna Weldon reviewed gene: TUBB4A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.264 TH Kaitlyn Dianna Weldon reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301334, 20301610; Phenotypes: TH-deficient dopa-responsive dystonia MONDO:0011551, tyrosine hydroxylase deficiency MONDO:0100064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.264 SPR Claire Fryer-Smith reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: 22522443, 11920285, 14663042, 16443856, 21782285, 32813147; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (MIM# 612716); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.264 SPG11 Claire Fryer-Smith reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 35036589, 23121729, 21381113, 27217339; Phenotypes: Amyotrophic lateral sclerosis 5, juvenile (MIM# 602099), Charcot-Marie-Tooth disease, axonal, type 2X (MIM# 616668), Spastic paraplegia 11, autosomal recessive (MIM# 604360); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.264 SLC30A10 Claire Fryer-Smith reviewed gene: SLC30A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22341971, 22341972; Phenotypes: Hypermanganesemia with dystonia 1 (MIM# 613280); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.264 SLC39A14 Zornitza Stark Phenotypes for gene: SLC39A14 were changed from to Hypermanganesemia with dystonia 2 (MIM# 617013)
Early-onset Parkinson disease v0.260 SLC39A14 Claire Fryer-Smith reviewed gene: SLC39A14: Rating: GREEN; Mode of pathogenicity: None; Publications: 27231142, 32626807, 29685658, 30232769; Phenotypes: Hypermanganesemia with dystonia 2 (MIM# 617013); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.260 RAB39B Claire Fryer-Smith reviewed gene: RAB39B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25434005, 26399558, 26739247; Phenotypes: Waisman syndrome (MIM#311510), Intellectual developmental disorder, X-linked 72 (MIM#300271); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.260 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from pantothenate kinase-associated neurodegeneration MONDO:0009319 to pantothenate kinase-associated neurodegeneration MONDO:0009319
Early-onset Parkinson disease v0.259 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from pantothenate kinase-associated neurodegeneration MONDO:0009319 to pantothenate kinase-associated neurodegeneration MONDO:0009319
Early-onset Parkinson disease v0.258 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from to pantothenate kinase-associated neurodegeneration MONDO:0009319
Early-onset Parkinson disease v0.252 POLG Zornitza Stark Phenotypes for gene: POLG were changed from to autosomal dominant progressive external ophthalmoplegia MONDO:0008003
Early-onset Parkinson disease v0.243 PSEN1 Kaitlyn Dianna Weldon reviewed gene: PSEN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 3548932, 34843019, 36825052; Phenotypes: early-onset parkinsons disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 PRNP Kaitlyn Dianna Weldon reviewed gene: PRNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301407; Phenotypes: inherited Creutzfeldt-Jakob disease MONDO:0007403, Gerstmann-Straussler-Scheinker syndrome MONDO:0007656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 PRKRA Kaitlyn Dianna Weldon reviewed gene: PRKRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 33502045; Phenotypes: dystonia 16 MONDO:0012789; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 POLG Kaitlyn Dianna Weldon reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301791, 15351195; Phenotypes: autosomal dominant progressive external ophthalmoplegia MONDO:0008003; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 PLA2G6 Kaitlyn Dianna Weldon reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301718; Phenotypes: autosomal recessive Parkinson disease 14 MONDO:0013060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 PANK2 Kaitlyn Dianna Weldon edited their review of gene: PANK2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 PARK7 Kaitlyn Dianna Weldon reviewed gene: PARK7: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301402; Phenotypes: Parkinson disease MONDO:0005180, autosomal recessive early-onset Parkinson disease 7 MONDO:0011658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 PANK2 Kaitlyn Dianna Weldon reviewed gene: PANK2: Rating: ; Mode of pathogenicity: None; Publications: 23447832, 20301663; Phenotypes: pantothenate kinase-associated neurodegeneration MONDO:0009319; Mode of inheritance: None
Early-onset Parkinson disease v0.243 MAPT Kaitlyn Dianna Weldon reviewed gene: MAPT: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301678; Phenotypes: late-onset Parkinson disease MONDO:0008199; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 LYST Kaitlyn Dianna Weldon reviewed gene: LYST: Rating: GREEN; Mode of pathogenicity: None; Publications: 23436631, 23521865, 20301751; Phenotypes: Chediak-Higashi syndrome MONDO:0008963; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 LRRK2 Kaitlyn Dianna Weldon reviewed gene: LRRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301387; Phenotypes: autosomal dominant Parkinson disease 8 MONDO:0011764, obsolete hereditary late onset Parkinson disease MONDO:0018466, Parkinson disease MONDO:0005180; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 FTL Kaitlyn Dianna Weldon edited their review of gene: FTL: Changed rating: GREEN
Early-onset Parkinson disease v0.243 FTL Kaitlyn Dianna Weldon reviewed gene: FTL: Rating: ; Mode of pathogenicity: None; Publications: 23447832, 20301320; Phenotypes: neuroferritinopathy MONDO:0011638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 FBXO7 Kaitlyn Dianna Weldon reviewed gene: FBXO7: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301402; Phenotypes: parkinsonian-pyramidal syndrome MONDO:0009830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 DNAJC6 Kaitlyn Dianna Weldon reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 33983693; Phenotypes: juvenile onset Parkinson disease 19A MONDO:0014231; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 OPA3 Kaitlyn Dianna Weldon reviewed gene: OPA3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.243 DCTN1 Kaitlyn Dianna Weldon reviewed gene: DCTN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20945553; Phenotypes: Perry syndrome MONDO:0008201; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 CSF1R Kaitlyn Dianna Weldon reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 25935893, 22934315; Phenotypes: obsolete hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia MONDO:0009096; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 C19orf12 Kaitlyn Dianna Weldon reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780, 23278385; Phenotypes: neurodegeneration with brain iron accumulation 4 MONDO:0013674; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 ATP1A3 Kaitlyn Dianna Weldon reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17282997, 15260953, 17595045, 17516473, 22534615; Phenotypes: ATP1A3-associated neurological disorder MONDO:0700002; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.243 ATP13A2 Kaitlyn Dianna Weldon reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25900096; Phenotypes: parkinsonism due to ATP13A2 deficiency MONDO:0017809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.242 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.241 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.241 PTPA Zornitza Stark Mode of inheritance for gene: PTPA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.240 PTPA Ee Ming Wong reviewed gene: PTPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 37448355; Phenotypes: Intellectual disability, MONDO: 36073231, PTPA-related, Parkisonism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Early-onset Parkinson disease v0.240 ATP7B Sangavi Sivagnanasundram reviewed gene: ATP7B: Rating: AMBER; Mode of pathogenicity: None; Publications: 31426520, 33972609, 36553628, 16737839; Phenotypes: Wilson disease (MONDO:0010200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early-onset Parkinson disease v0.237 GIGYF2 Bryony Thompson reviewed gene: GIGYF2: Rating: RED; Mode of pathogenicity: None; Publications: 18358451, 33239198, 25279164, 20060621, 19250854, 26152800; Phenotypes: {Parkinson disease 11} , OMIM # 607688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.232 AFG3L2 Zornitza Stark reviewed gene: AFG3L2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 28, MIM# 610246; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.232 AFG3L2 Shekeeb Mohammad reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36110148; Phenotypes: dystonia, parkinsonism, intellectual disability, optic hypoplasia, cognitive decline, dementia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Early-onset Parkinson disease v0.231 PTPA Zornitza Stark gene: PTPA was added
gene: PTPA was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PTPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPA were set to 36073231
Phenotypes for gene: PTPA were set to Intellectual disability, MONDO: 36073231, PTPA-related; Parkisonism
Review for gene: PTPA was set to AMBER
Added comment: Biallelic PTPA pathogenic variants lead to a form of ID with later-onset parkinsonism based on 4 individuals from 2 families in the literature. Affected individuals were homozygous for missense variants demonstrated to result to reduced mRNA and protein levels as well as PP2A complex activation. Drosophila studies support an age-dependent locomotor dysfunction. Variants in other PP2A-complex-related genes also lead to NDDs. Summary provided below.

There is currently no associated phenotype in OMIM, G2P, PanelApp UK or SysID.

Consider inclusion in relevant panels (ID, Parkinsonism/movement disorders, etc) with amber rating pending further reports.

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Fevga, Tesson et al (2022 - PMID: 36073231) describe the features of 4 individuals, from 2 unrelated families, with biallelic pathogenic PTPA variants.

These presented with normal or delayed early milestones, learning disability and ID (mild to moderate) followed by progressive signs of parkinsonism (at the age of 11 yrs in 2 sibs, 15 yrs in another individual). Motor symptoms were responsive to levodopa and later to deep brain stimulation.

Linkage analysis in one consanguineous family followed by exome revealed homozygosity for a missense PTPA variant (NM_178001:c.893T>G/p.Met298Arg). Exome sequencing in affected subjects from the 2nd family revealed homozygosity for a further missense variant (c.512C>A/p.Ala171Asp). There were no other candidate variants for the phenotype following parental / segregation studies.

Role of the gene:
As the authors discuss, PTPA (or PPP2R4) is ubiquitously expressed in all tissues incl. brain and encodes a phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase-2A (PP2A). PP2A in turn, is the major Ser/Thr phosphatase in brain targeting a large number of proteins involved in diverse functions. Activation of PP2A is dependent on its methylation, which is negatively regulated by the PP2A-specific methylesterase (PME-1). By binding to PME-1, PTPA counteracts the negative influence of the former on PP2A. Pathogenic variants in genes encoding subunits/regulators of the PP2A complex (e.g. PPP2R1A or PPP2CA) are associated with neurodevelopmental disorders.

Variant studies:
Upon overexpression of wt and both variants in a HEK-293 cell line the authors demonstrated that both variants resulted in significantly reduced mRNA and protein levels (which for Ala171Asp were attributed to increased proteasomal degradation). Both variants were shown to result in impaired PP2A complex activation compared to wt.

Drosophila / animal models:
Pan-neuronal RNAi-mediated knockdown of ptpa in Drosophila resulted in an age-dependent locomotor dysfunction, reversible with L-DOPA treatment.
Previous studies in mice suggest cognitive/electrophysiological impairments upon downregulation of PP2A activity in transgenic mice.
Sources: Literature
Early-onset Parkinson disease v0.227 WASL Zornitza Stark reviewed gene: WASL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson's disease, MONDO:0005180, WASL-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.227 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from DYT28; Childhood‐onset and progressive dystonia; Dysarthria; Dysphagia; Developmental delay; Dysmorphic features; Parkinsonism; OMIM 617284 to Dystonia 28, childhood-onset , MIM#617284
Early-onset Parkinson disease v0.224 KMT2B Zornitza Stark reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 28, childhood-onset , MIM#617284; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.220 GBA Zornitza Stark reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 35639160; Phenotypes: Parkinson's disease, MONDO:0005180, GBA-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.220 FRRS1L Zornitza Stark Phenotypes for gene: FRRS1L were changed from Developmental and epileptic dyskinetic encephalopathy; Seizures; Chorea; Parkinsonism; Developmental delay; OMIM 616981 to Developmental and epileptic encephalopathy 37, MIM# 616981; Seizures; Chorea; Parkinsonism; Developmental delay
Early-onset Parkinson disease v0.218 FRRS1L Zornitza Stark reviewed gene: FRRS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 37, MIM# 616981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.216 ALPL Zornitza Stark reviewed gene: ALPL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypophosphatasia, adult, MIM# 146300; Mode of inheritance: None
Early-onset Parkinson disease v0.215 KMT2B SHEKEEB MOHAMMAD gene: KMT2B was added
gene: KMT2B was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2B were set to PMID: 33816656
Phenotypes for gene: KMT2B were set to DYT28; Childhood‐onset and progressive dystonia; Dysarthria; Dysphagia; Developmental delay; Dysmorphic features; Parkinsonism; OMIM 617284
Review for gene: KMT2B was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 FRRS1L SHEKEEB MOHAMMAD gene: FRRS1L was added
gene: FRRS1L was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FRRS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRRS1L were set to PMID: 29086067
Phenotypes for gene: FRRS1L were set to Developmental and epileptic dyskinetic encephalopathy; Seizures; Chorea; Parkinsonism; Developmental delay; OMIM 616981
Review for gene: FRRS1L was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 ALPL SHEKEEB MOHAMMAD gene: ALPL was added
gene: ALPL was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ALPL was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ALPL were set to PMID: 32956941
Phenotypes for gene: ALPL were set to Hypophosphatasia; Osteomalacia; Parkinsonism; OMIM 146300
Review for gene: ALPL was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 ADAR SHEKEEB MOHAMMAD gene: ADAR was added
gene: ADAR was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ADAR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAR were set to PMID: 32911246
Phenotypes for gene: ADAR were set to Aicardi-Goutieres syndrome 6; neuroinflammatory disorder with cerebral calcification; progressive loss of cognition; spasticity; dystonia; parkinsonism; OMIM 615010
Review for gene: ADAR was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Primary familial brain calcification; Atypical parkinsonism; Supranuclear gaze palsy; OMIM 618317 to Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM #618317; Primary familial brain calcification; Atypical parkinsonism; Supranuclear gaze palsy
Early-onset Parkinson disease v0.212 KIAA1161 Zornitza Stark reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: None; Publications: 30656188, 30649222, 30460687, 29910000, 31951047; Phenotypes: Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM #618317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.210 NHLRC1 Zornitza Stark reviewed gene: NHLRC1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 2B (Lafora), MIM# 254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.208 C9orf3 Zornitza Stark reviewed gene: C9orf3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35306330; Phenotypes: Dystonia 31, MIM# 619565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark Gene: atxn10 has been removed from the panel.
Early-onset Parkinson disease v0.208 ATXN2 Zornitza Stark Gene: atxn2 has been removed from the panel.
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark Gene: atxn3 has been removed from the panel.
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark Gene: atxn8 has been removed from the panel.
Early-onset Parkinson disease v0.205 TPP1 Zornitza Stark reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.205 CYP27A1 Zornitza Stark Phenotypes for gene: CYP27A1 were changed from Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy; OMIM 213700 to Cerebrotendinous xanthomatosis, MIM# 213700; Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy
Early-onset Parkinson disease v0.201 DDC Zornitza Stark reviewed gene: DDC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aromatic L-amino acid decarboxylase deficiency, MIM# 608643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.201 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Myoclonic Epilepsy; Parkinsonism; Ataxia; Intellectual disability; OMIM 617836 to Developmental delay and seizures with or without movement abnormalities, MIM# 617836; Myoclonic Epilepsy; Parkinsonism; Ataxia; Intellectual disability
Early-onset Parkinson disease v0.198 DHDDS Zornitza Stark reviewed gene: DHDDS: Rating: AMBER; Mode of pathogenicity: None; Publications: 34837344; Phenotypes: Developmental delay and seizures with or without movement abnormalities, MIM# 617836; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.198 EIF2AK2 Zornitza Stark Phenotypes for gene: EIF2AK2 were changed from Neurodevelopmental Syndrome; Developmental delays; Ataxia; Parkinsonism; White matter alterations; OMIM 618877 to Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877; Neurodevelopmental Syndrome; Developmental delays; Ataxia; Parkinsonism; White matter alterations
Early-onset Parkinson disease v0.195 EIF2AK2 Zornitza Stark reviewed gene: EIF2AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.193 EPM2A Zornitza Stark reviewed gene: EPM2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 2A (Lafora), MIM# 254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.192 FOXG1 Zornitza Stark Gene: foxg1 has been removed from the panel.
Early-onset Parkinson disease v0.192 FOXG1 Zornitza Stark Phenotypes for gene: FOXG1 were changed from Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies; OMIM 613454 to Rett syndrome, congenital variant, MIM# 613454; Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies
Early-onset Parkinson disease v0.189 GLB1 Zornitza Stark reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GM1-gangliosidosis, type III , MIM#230650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.189 C9orf3 SHEKEEB MOHAMMAD reviewed gene: C9orf3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark edited their review of gene: HEXA: Changed rating: RED; Changed phenotypes: Tay-Sachs disease, MIM# 272800; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.187 HEXA Zornitza Stark reviewed gene: HEXA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark Gene: jph3 has been removed from the panel.
Early-onset Parkinson disease v0.183 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.181 NPC1 Zornitza Stark reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Niemann-Pick disease, MIM# 257220; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.181 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Mental retardation 55 with seizures (MRD55); Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus; OMIM 617831 to Intellectual developmental disorder, autosomal dominant 55, with seizures, MIM# 617831; Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus
Early-onset Parkinson disease v0.178 PGK1 Zornitza Stark Phenotypes for gene: PGK1 were changed from Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653 to Phosphoglycerate kinase 1 deficiency, MIM# 300653; Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653
Early-onset Parkinson disease v0.176 PGK1 Zornitza Stark reviewed gene: PGK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Phosphoglycerate kinase 1 deficiency, MIM# 300653; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.176 POLR3A Zornitza Stark Phenotypes for gene: POLR3A were changed from POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism, OMIM 607694 to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism
Early-onset Parkinson disease v0.174 POLR3A Zornitza Stark reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark Gene: ppp2r2b has been removed from the panel.
Early-onset Parkinson disease v0.171 PRKCG Zornitza Stark reviewed gene: PRKCG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 14, MIM# 605361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.169 QDPR Zornitza Stark reviewed gene: QDPR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphenylalaninemia, BH4-deficient, C, MIM#261630; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.166 SCN1A Zornitza Stark reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dravet syndrome, MIM# 607208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.166 SERAC1 Zornitza Stark Phenotypes for gene: SERAC1 were changed from MEGDEL Syndrome; Parkinsonism to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, MIM# 614739; Parkinsonism
Early-onset Parkinson disease v0.164 SERAC1 Zornitza Stark reviewed gene: SERAC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, MIM# 614739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.164 SLC19A3 Zornitza Stark Phenotypes for gene: SLC19A3 were changed from Biotin-Thiamine Responsive Basal Ganglia disease; Childhood onset Dystonia and Parkinsonism; OMIM 607483 to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Childhood onset Dystonia and Parkinsonism
Early-onset Parkinson disease v0.162 SLC19A3 Zornitza Stark reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.159 SLC18A2 Zornitza Stark reviewed gene: SLC18A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23363473, 31240161, 26497564; Phenotypes: Parkinsonism-dystonia, infantile, 2 , MIM# 618049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.155 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from Hereditary Spastic Paraplegia 7; Ataxia; Progressive external opthalmoplegia; Parkinsonism; OMIM 607259 to Spastic paraplegia 7, autosomal recessive, MIM# 607259; Ataxia; Progressive external opthalmoplegia; Parkinsonism
Early-onset Parkinson disease v0.150 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Developmental and epileptic encephalopathy 4; Juvenile onset Parkinsonism; OMIM 612164 to Developmental and epileptic encephalopathy 4, MIM# 612164; Juvenile onset Parkinsonism
Early-onset Parkinson disease v0.146 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.146 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from Developmental and epileptic encephalopathy 16; Intellectual disability; Parkinsonism; Seizures; Psychosis; OMIM 615338 to Developmental and epileptic encephalopathy 16, MIM# 615338; Intellectual disability; Parkinsonism; Seizures; Psychosis
Early-onset Parkinson disease v0.144 TBC1D24 Zornitza Stark reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 16, MIM# 615338; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.144 TBP Zornitza Stark Gene: tbp has been removed from the panel.
Early-onset Parkinson disease v0.144 UBTF Zornitza Stark Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset; Parkinsonism; Dystonia; Chorea; Brain atrophy to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; Parkinsonism; Dystonia; Chorea; Brain atrophy
Early-onset Parkinson disease v0.141 UBTF Zornitza Stark reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.139 VAC14 Zornitza Stark reviewed gene: VAC14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Striatonigral degeneration, childhood-onset, MIM# 617054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.136 WARS2 Zornitza Stark reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34890876, 31970218, 29120065; Phenotypes: Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.134 CYP27A1 SHEKEEB MOHAMMAD gene: CYP27A1 was added
gene: CYP27A1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to PMID: 30054180
Phenotypes for gene: CYP27A1 were set to Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy; OMIM 213700
Review for gene: CYP27A1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 FOXG1 SHEKEEB MOHAMMAD gene: FOXG1 was added
gene: FOXG1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FOXG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXG1 were set to PMID: 21953941
Phenotypes for gene: FOXG1 were set to Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies; OMIM 613454
Review for gene: FOXG1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 NPC1 SHEKEEB MOHAMMAD edited their review of gene: NPC1: Changed publications: PMID: 24035292, 30369906
Early-onset Parkinson disease v0.134 NUS1 SHEKEEB MOHAMMAD gene: NUS1 was added
gene: NUS1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NUS1 were set to PMID: 32485575; 30348779
Phenotypes for gene: NUS1 were set to Mental retardation 55 with seizures (MRD55); Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus; OMIM 617831
Review for gene: NUS1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 PGK1 SHEKEEB MOHAMMAD gene: PGK1 was added
gene: PGK1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PGK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PGK1 were set to PMID: 30975619
Phenotypes for gene: PGK1 were set to Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653
Review for gene: PGK1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 POLR3A SHEKEEB MOHAMMAD gene: POLR3A was added
gene: POLR3A was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to PMID: 33652360
Phenotypes for gene: POLR3A were set to POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism, OMIM 607694
Review for gene: POLR3A was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SLC19A3 SHEKEEB MOHAMMAD gene: SLC19A3 was added
gene: SLC19A3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC19A3 were set to PMID: 24260777
Phenotypes for gene: SLC19A3 were set to Biotin-Thiamine Responsive Basal Ganglia disease; Childhood onset Dystonia and Parkinsonism; OMIM 607483
Review for gene: SLC19A3 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SPG7 SHEKEEB MOHAMMAD gene: SPG7 was added
gene: SPG7 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to PMID: 31433872
Phenotypes for gene: SPG7 were set to Hereditary Spastic Paraplegia 7; Ataxia; Progressive external opthalmoplegia; Parkinsonism; OMIM 607259
Review for gene: SPG7 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 STXBP1 SHEKEEB MOHAMMAD gene: STXBP1 was added
gene: STXBP1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: STXBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: STXBP1 were set to PMID: 25418441, 32643187, 29929108
Phenotypes for gene: STXBP1 were set to Developmental and epileptic encephalopathy 4; Juvenile onset Parkinsonism; OMIM 612164
Review for gene: STXBP1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 TBC1D24 SHEKEEB MOHAMMAD gene: TBC1D24 was added
gene: TBC1D24 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: TBC1D24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D24 were set to PMID: 28663785; 21087195
Phenotypes for gene: TBC1D24 were set to Developmental and epileptic encephalopathy 16; Intellectual disability; Parkinsonism; Seizures; Psychosis; OMIM 615338
Review for gene: TBC1D24 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 WARS2 SHEKEEB MOHAMMAD reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.134 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
Early-onset Parkinson disease v0.132 GIGYF2 Chirag Patel gene: GIGYF2 was added
gene: GIGYF2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: GIGYF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIGYF2 were set to PMID: 18358451, 19449032
Phenotypes for gene: GIGYF2 were set to {Parkinson disease 11} , OMIM # 607688
Review for gene: GIGYF2 was set to AMBER
Added comment: In affected members of 12 unrelated Italian or French families with Parkinson disease-11 (PARK11; 607688), Lautier et al. (2008) identified 7 different heterozygous mutations in the GIGYF2 gene. Tan et al. (2009) identified 4 different heterozygous mutations in the GIGYF2 gene in 7 (1.6%) of 450 patients with Parkinson disease from Taiwan and Singapore. The mutations were not identified in 400 controls. Reduced penetrance seen in the families reported by both groups. No replication since.
Sources: Literature
Early-onset Parkinson disease v0.130 FXTAS Bryony Thompson STR: FXTAS was added
STR: FXTAS was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for STR: FXTAS 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 STR: FXTAS were set to 27340021; 28176767; 20301558; 23765048; 25227148; 11445641
Phenotypes for STR: FXTAS were set to Fragile X tremor/ataxia syndrome MIM#300623
Review for STR: FXTAS was set to GREEN
STR: FXTAS was marked as clinically relevant
Added comment: Parkinsonism is a common feature of FXTAS, which is associated with the premutation.
HGVS nomenclature - NM_002024.5:c.-129_-127CGG[X]
RNA-mediated toxicity may result in the FXTAS phenotype, whereas loss of function through methylation silencing of FMR1 is associated with the FXS phenotype.
Intermediate (grey zone, inconclusive, borderline): ~45 to ~54 repeats
Premutation - risk of FXTAS: ~55 to ~200 repeats
Full mutation - fragile X syndrome (FXS): >200 repeats
Sources: Literature
Early-onset Parkinson disease v0.127 FMR1 Bryony Thompson changed review comment from: Parkinsonism can be a relatively common feature of the condition. The major cause of the condition is 5'UTR repeat expansion, but at least 6 pathogenic intragenic SNV or small indels have been reported in affected males.; to: Parkinsonism can be a relatively common feature of FXTAS, which is caused by 5'UTR repeat expansion.
Early-onset Parkinson disease v0.127 FMR1 Bryony Thompson edited their review of gene: FMR1: Changed publications: 27340021, 28176767, 20301558; Changed phenotypes: Fragile X tremor/ataxia syndrome MIM#300623
Early-onset Parkinson disease v0.127 FMR1 Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a feature of FXTAS and is not reported in cases with intragenic variants, which have the FXS phenotype. Added as an STR.
Early-onset Parkinson disease v0.127 FMR1 Bryony Thompson Gene: fmr1 has been removed from the panel.
Early-onset Parkinson disease v0.123 SYNJ1 Zornitza Stark reviewed gene: SYNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23804563, 23804577, 27496670, 33841314; Phenotypes: Parkinson disease 20, early-onset, MIM# 615530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.120 VPS35 Zornitza Stark reviewed gene: VPS35: Rating: GREEN; Mode of pathogenicity: None; Publications: 21763482, 21763483, 22801713, 34704029; Phenotypes: Parkinson disease 17, MIM# 614203; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.119 NIID Bryony Thompson STR: NIID was added
STR: NIID was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102; 34333668
Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Oculopharyngodistal myopathy 3 MIM#619473; Tremor, hereditary essential, 6 MIM#618866
Review for STR: NIID was set to GREEN
STR: NIID was marked as clinically relevant
Added comment: NM_001364012.2:c.-164GGC[X]
Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2.
Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease.
Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier.
Intermediate range: 41-60 identified in Parkinson's disease
Pathogenic repeat range: >=60-520
Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Literature
Early-onset Parkinson disease v0.118 Bryony Thompson removed STR:NIID from the panel
Early-onset Parkinson disease v0.117 TAF1 Bryony Thompson Added comment: Comment on list classification: Added as an STR to the panel
Early-onset Parkinson disease v0.117 TAF1 Bryony Thompson Gene: taf1 has been removed from the panel.
Early-onset Parkinson disease v0.115 XDP Bryony Thompson STR: XDP was added
STR: XDP was added to Early-onset Parkinson disease. Sources: Expert list
founder tags were added to STR: XDP.
Mode of inheritance for STR: XDP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: XDP were set to 17273961; 29229810
Phenotypes for STR: XDP were set to Dystonia-Parkinsonism, X-linked MIM#314250
Review for STR: XDP was set to GREEN
STR: XDP was marked as clinically relevant
Added comment: Founder Filipino variant. Associated with an antisense insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon within an intron. The number of repeats in these cases ranged from 35 to 52 and showed a highly significant inverse correlation with age at disease onset. The mechanism of disease is unknown, possibly this intronic retroelement may induce transcriptional interference in TAF1 expression.
Sources: Expert list
Early-onset Parkinson disease v0.113 FTDALS Bryony Thompson STR: FTDALS was added
STR: FTDALS was added to Early-onset Parkinson disease. 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 25577942; 21944779; 21944778; 31779815
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
Early-onset Parkinson disease v0.112 Bryony Thompson removed STR:C9orf72 from the panel
Early-onset Parkinson disease v0.110 PSAP Zornitza Stark reviewed gene: PSAP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease 24, autosomal dominant, susceptibility to, MIM# 619491; Mode of inheritance: None
Early-onset Parkinson disease v0.108 FMR1 Bryony Thompson Mode of inheritance for gene: FMR1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.106 NIID Bryony Thompson STR: NIID was added
STR: NIID was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102
Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Tremor, hereditary essential, 6 MIM#618866
Review for STR: NIID was set to GREEN
STR: NIID was marked as clinically relevant
Added comment: NM_001364012.2:c.-164GGC[(66_517)] Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease. Normal repeat range: 7-60 Pathogenic repeat range: >=61-500 Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Literature
Early-onset Parkinson disease v0.102 PINK1 Elena Savva reviewed gene: PINK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28980524; Phenotypes: Parkinson disease 6, early onset MIM#605909; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.102 UQCRC1 Zornitza Stark Phenotypes for gene: UQCRC1 were changed from Parkinson's disease to Parkinsonism with polyneuropathy, MIM# 619279
Early-onset Parkinson disease v0.101 UQCRC1 Zornitza Stark edited their review of gene: UQCRC1: Changed phenotypes: Parkinsonism with polyneuropathy, MIM# 619279
Early-onset Parkinson disease v0.98 PSAP Ain Roesley changed review comment from: 6 affecteds from 3 families. Age of onset ranges from 33-60.
Functional studies: Autophagic vacuole accumulation in skin fibroblasts , a-Synuclein aggregation and PSAP retention in the ER and abnormal intracellular accumulation in iPSC-dopaminergic neurons. Mouse model for one of 1 of the variants had motor deficits and dopaminergic neurodegeneration
Sources: Literature; to: - 6 affecteds from 3 families. Age of onset ranges from 33-60.
- 2x missense and 1 inframe del
- Functional studies: Autophagic vacuole accumulation in skin fibroblasts , a-Synuclein aggregation and PSAP retention in the ER and abnormal intracellular accumulation in iPSC-dopaminergic neurons. Mouse model for one of 1 of the variants had motor deficits and dopaminergic neurodegeneration
Sources: Literature
Early-onset Parkinson disease v0.98 PSAP Ain Roesley gene: PSAP was added
gene: PSAP was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PSAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PSAP were set to 32201884
Phenotypes for gene: PSAP were set to parkinson's disease
Penetrance for gene: PSAP were set to unknown
Review for gene: PSAP was set to GREEN
Added comment: 6 affecteds from 3 families. Age of onset ranges from 33-60.
Functional studies: Autophagic vacuole accumulation in skin fibroblasts , a-Synuclein aggregation and PSAP retention in the ER and abnormal intracellular accumulation in iPSC-dopaminergic neurons. Mouse model for one of 1 of the variants had motor deficits and dopaminergic neurodegeneration
Sources: Literature
Early-onset Parkinson disease v0.97 NR4A2 Sebastian Lunke gene: NR4A2 was added
gene: NR4A2 was added to Early-onset Parkinson disease. 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
Early-onset Parkinson disease v0.95 PPP2R5D Zornitza Stark gene: PPP2R5D was added
gene: PPP2R5D was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R5D were set to 33338668; 32743835
Phenotypes for gene: PPP2R5D were set to Early onset Parkinsonism; Mental retardation, autosomal dominant 35, MIM# 616355
Review for gene: PPP2R5D was set to GREEN
Added comment: 5 individuals reported with de novo missense variants in this gene, a neurodevelopmental disorder, and onset of parkinsonism between the ages of 20-40 years. Four had the same p.(Glu200Lys) variant, and the fifth had p.(Glu198Lys)
Sources: Literature
Early-onset Parkinson disease v0.93 UQCRC1 Zornitza Stark gene: UQCRC1 was added
gene: UQCRC1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: UQCRC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UQCRC1 were set to 33141179; 33248804
Phenotypes for gene: UQCRC1 were set to Parkinson's disease
Review for gene: UQCRC1 was set to AMBER
Added comment: Three unrelated families reported in PMID 33141179 with some functional data, however PMID 33248804 failed to identify significant variants in this gene in a large PD cohort.
Sources: Literature
Early-onset Parkinson disease v0.89 SNCA Ain Roesley reviewed gene: SNCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 32849182, 26858591, 32740728; Phenotypes: Dementia, Lewy body (MIM#127750), Parkinson disease 1 (MIM#168601), Parkinson disease 4 (MIM#605543); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.88 C9orf72 Bryony Thompson STR: C9orf72 was added
STR: C9orf72 was added to Early-onset Parkinson disease. 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 25577942; 31779815
Phenotypes for STR: C9orf72 were set to 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
Early-onset Parkinson disease v0.87 C9orf72 Bryony Thompson Gene: c9orf72 has been removed from the panel.
Early-onset Parkinson disease v0.86 HTT Bryony Thompson Gene: htt has been removed from the panel.
Early-onset Parkinson disease v0.85 RIC3 Bryony Thompson gene: RIC3 was added
gene: RIC3 was added to Early-onset Parkinson disease. Sources: Other
Mode of inheritance for gene: RIC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RIC3 were set to 27055476; 28153381; 28606768; 32794657
Phenotypes for gene: RIC3 were set to Parkinson disease
Review for gene: RIC3 was set to RED
Added comment: Segregation reported in a single Indian family (PMID: 27055476), with limited in vitro functional assays. The variant is present in the South Asian population in gnomAD v2.1 14/30,596 alleles. The association has not been replicated in any additional studies.
Sources: Other
Early-onset Parkinson disease v0.84 XPR1 Zornitza Stark Phenotypes for gene: XPR1 were changed from to Basal ganglia calcification, idiopathic, 6, MIM# 616413
Early-onset Parkinson disease v0.81 XPR1 Zornitza Stark reviewed gene: XPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25938945; Phenotypes: Basal ganglia calcification, idiopathic, 6, MIM# 616413; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.80 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286
Early-onset Parkinson disease v0.75 TAF1 Zornitza Stark reviewed gene: TAF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 17273961; Phenotypes: Dystonia-Parkinsonism, X-linked, MIM# 314250; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.75 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from to Basal ganglia calcification, idiopathic, 4, MIM# 615007
Early-onset Parkinson disease v0.72 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255827, 30979360; Phenotypes: Basal ganglia calcification, idiopathic, 4 615007; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.72 PDGFB Zornitza Stark Phenotypes for gene: PDGFB were changed from to Basal ganglia calcification, idiopathic, 5, MIM# 615483
Early-onset Parkinson disease v0.69 PDGFB Zornitza Stark reviewed gene: PDGFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23913003; Phenotypes: Basal ganglia calcification, idiopathic, 5, MIM# 615483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.66 MECP2 Zornitza Stark reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31970230, 27050783; Phenotypes: MECP2-related disorders, Rett syndrome, MIM# 312750, Mental retardation, X-linked, syndromic 13, MIM# 300055; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.66 GRN Zornitza Stark Phenotypes for gene: GRN were changed from to Frontotemporal lobar degeneration with ubiquitin-positive inclusions, MIM# 607485
Early-onset Parkinson disease v0.63 GRN Zornitza Stark reviewed gene: GRN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17923627, 20301545; Phenotypes: Frontotemporal lobar degeneration with ubiquitin-positive inclusions, MIM# 607485; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.63 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from to Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230
Early-onset Parkinson disease v0.60 GCH1 Zornitza Stark reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32170445, 32278297, 32746945, 30314816; Phenotypes: Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.57 DNAJC5 Zornitza Stark reviewed gene: DNAJC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22978711, 21820099, 22235333; Phenotypes: Ceroid lipofuscinosis, neuronal, 4, Parry type, MIM# 162350; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.57 CLN3 Zornitza Stark reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 3 MIM#204200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.57 SLC20A2 Zornitza Stark Phenotypes for gene: SLC20A2 were changed from to Basal ganglia calcification, idiopathic, 1, MIM# 213600
Early-onset Parkinson disease v0.54 SLC20A2 Zornitza Stark reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22327515, 23334463; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.54 COASY Zornitza Stark Phenotypes for gene: COASY were changed from to Neurodegeneration with brain iron accumulation 6, MIM# 615643
Early-onset Parkinson disease v0.50 COASY Zornitza Stark reviewed gene: COASY: Rating: AMBER; Mode of pathogenicity: None; Publications: 28489334, 24360804; Phenotypes: Neurodegeneration with brain iron accumulation 6, MIM# 615643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.41 APP Zornitza Stark reviewed gene: APP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Alzheimer disease 1, familial, MIM# 104300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.40 HD Bryony Thompson STR: HD was added
STR: HD was added to Early-onset Parkinson disease. Sources: Expert list
STR tags were added to STR: HD.
Mode of inheritance for STR: HD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HD were set to 20301482; 29325606
Phenotypes for STR: HD were set to Huntington disease MIM#143100
Review for STR: HD was set to GREEN
STR: HD was marked as clinically relevant
Added comment: NM_002111.8:c.52_54CAG[X]
Primary mechanism of disease is gain of function
Normal: ≤26 repeats
Intermediate: 27-35 repeats, no risk for proband but expansion possible in the next generation
Pathogenic (reduced penetrance): 36-39 repeats, proband at risk for HD but may not develop symptoms
Pathogenic (full penetrance): ≥40 repeats, development of HD with increased certainty assuming a normal life span
Sources: Expert list
Early-onset Parkinson disease v0.39 Bryony Thompson removed STR:HD from the panel
Early-onset Parkinson disease v0.37 HD Bryony Thompson STR: HD was added
STR: HD was added to Early-onset Parkinson disease. Sources: Expert list
STR tags were added to STR: HD.
Mode of inheritance for STR: HD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HD were set to 20301482; 29325606
Phenotypes for STR: HD were set to Huntington disease MIM#143100
Review for STR: HD was set to GREEN
STR: HD was marked as clinically relevant
Added comment: NM_002111.8:c.52_54CAG[X]
Primary mechanism of disease is gain of function
Normal: ≤26 repeats
Intermediate: 27-35 repeats, no risk for proband but expansion possible in the next generation
Pathogenic (reduced penetrance): 36-39 repeats, proband at risk for HD but may not develop symptoms
Pathogenic (full penetrance): ≥40 repeats, development of HD with increased certainty assuming a normal life span
Sources: Expert list
Early-onset Parkinson disease v0.33 SLC6A3 Zornitza Stark reviewed gene: SLC6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21112253; Phenotypes: Parkinsonism-dystonia, infantile, 1, MIM# 613135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.32 ATP6AP2 Zornitza Stark gene: ATP6AP2 was added
gene: ATP6AP2 was added to Early-onset Parkinson disease. Sources: Expert list
Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP2 were set to 30985297; 23595882
Phenotypes for gene: ATP6AP2 were set to Parkinsonism with spasticity, X-linked, MIM# 300911
Review for gene: ATP6AP2 was set to GREEN
Added comment: PMID: 30985297 - 1 de novo male patient with postnatal neurodegeneration, seizures, mild face dysmorphism. Sequential MRI revealed decreasing gray and white matter volumes. Patient has a splice variant proven to cause alternative transcript expression. Supported by null mouse model.

PMID: 23595882 - 2 patients (1 family) with a synonymous variant proven to affect splicing. Patients have X-linked parkinsonian syndrome

Summary: 2 unrelated patients + animal models
Sources: Expert list
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson changed review comment from: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic variants and a VUS (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other; to: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with VUS and parkinsonism as a feature of the condition and a single family with multiple members with parkinsonism with pathogenic missense variant have been reported (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson changed review comment from: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic or probable pathogenic variants (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other; to: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic variants and a VUS (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Early-onset Parkinson disease v0.31 PSEN2 Bryony Thompson gene: PSEN2 was added
gene: PSEN2 was added to Early-onset Parkinson disease. Sources: Other
Mode of inheritance for gene: PSEN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSEN2 were set to 22118943; 26422362; 18427071; 29692703
Phenotypes for gene: PSEN2 were set to Parkinsonism; Alzheimer disease-4 MIM#606889
Review for gene: PSEN2 was set to RED
Added comment: Parkinson disease and parkinsonism is not a prominent feature of Alzheimer disease caused by PSEN2. A couple of isolated cases with parkinsonism as a feature of the condition and a single family have been reported with established pathogenic or probable pathogenic variants (PMID: 22118943, 26422362, 18427071). VUS or now likely benign/benign missense variants have been identified in a Parkinson Disease cases used in case-control studies (PMID: 29692703, 26522186).
Sources: Other
Early-onset Parkinson disease v0.28 PODXL Bryony Thompson gene: PODXL was added
gene: PODXL was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PODXL was set to Unknown
Publications for gene: PODXL were set to 26864383; 20706633
Phenotypes for gene: PODXL were set to juvenile-onset Parkinson disease
Review for gene: PODXL was set to AMBER
Added comment: Single consanguineous Indian family reported with a homozygous loss of function variant. A Podxl null mouse model has aberrant neurite length and number of branching points, and also evidence of impaired synaptogenesis. Subsequent screening in 280 Parkinson disease patients with various ages of onset identified 3 heterozygous missense variants (P429T, S373N, and R294Q; all numbering according to isoform 2), absent in gnomAD. Transfection of the missense variants into PC12 cells resulted in variable aberrant neurite length and/or branching, suggesting a functional effect. However, there is more evidence supporting the association of monoallelic and biallelic variants with FSGS (see Proteinuria panel). There was no renal symptoms present in the reported family, which had renal function tests.
Sources: Literature
Early-onset Parkinson disease v0.25 VPS13C Bryony Thompson gene: VPS13C was added
gene: VPS13C was added to Early onset Parkinson disease. Sources: Expert list
Mode of inheritance for gene: VPS13C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13C were set to 26942284; 30452786; 28862745
Phenotypes for gene: VPS13C were set to Parkinson disease 23, autosomal recessive, early onset MIM#616840
Review for gene: VPS13C was set to GREEN
Added comment: >3 cases with biallelic variants.
Sources: Expert list
Early-onset Parkinson disease v0.23 TWNK Bryony Thompson reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: None; Publications: 24076137, 22949510, 22580846, 19353676; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.22 PTS Bryony Thompson reviewed gene: PTS: Rating: GREEN; Mode of pathogenicity: None; Publications: 11388593, 27562098; Phenotypes: Hyperphenylalaninemia, BH4-deficient, A MIM#261640; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.21 PTRHD1 Bryony Thompson gene: PTRHD1 was added
gene: PTRHD1 was added to Early onset Parkinson disease. Sources: Expert list
Mode of inheritance for gene: PTRHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTRHD1 were set to 27753167; 27134041; 30398675; 29143421
Phenotypes for gene: PTRHD1 were set to early-onset parkinsonism; intellectual disability
Review for gene: PTRHD1 was set to GREEN
Added comment: Homozygous variants segregate in three unrelated families from Iran and South Africa. No functional assays conducted.
Sources: Expert list
Early-onset Parkinson disease v0.19 KIF5A Bryony Thompson reviewed gene: KIF5A: Rating: AMBER; Mode of pathogenicity: None; Publications: 18853458; Phenotypes: Spastic paraplegia 10, autosomal dominant MIM#604187; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.19 C9orf72 Bryony Thompson Added comment: Comment on list classification: A repeat expansion is the cause of disease for this gene, which is currently not detectable by NGS.
Early-onset Parkinson disease v0.18 C9orf72 Bryony Thompson changed review comment from: Comment on list classification: A repeat expansion is the cause of disease for this gene, which is currently not detectable by NGS.; to: Parkinsonism is a common feature of the condition. A repeat expansion is the cause of disease for this gene.
Early-onset Parkinson disease v0.18 C9orf72 Bryony Thompson changed review comment from: Comment on list classification: A repeat expansion is the cause of disease for this gene, which is currently not detectable by NGS.; to: Comment on list classification: A repeat expansion is the cause of disease for this gene, which is currently not detectable by NGS.
Early-onset Parkinson disease v0.18 C9orf72 Bryony Thompson edited their review of gene: C9orf72: Changed rating: GREEN; Changed publications: 31779815; Changed phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MIM#105550; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.18 HTT Bryony Thompson Added comment: Comment on list classification: Parkinsonism is a feature of Huntingtons. This repeat expansion is not detectable by current NGS technology.
Early-onset Parkinson disease v0.17 HTT Bryony Thompson reviewed gene: HTT: Rating: GREEN; Mode of pathogenicity: None; Publications: 26740508, 27329733, 31800013; Phenotypes: Lopes-Maciel-Rodan syndrome MIM#617435, Huntington disease MIM#143100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.17 FMR1 Bryony Thompson reviewed gene: FMR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27340021, 28176767; Phenotypes: Fragile X tremor/ataxia syndrome MIM#300623, Fragile X syndrome MIM#300624; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Parkinson disease v0.17 TMEM230 Bryony Thompson gene: TMEM230 was added
gene: TMEM230 was added to Early onset Parkinson disease. Sources: Expert list
Mode of inheritance for gene: TMEM230 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM230 were set to 30804554; 27270108; 28115417; 28017548; 30804555; 30804556; 31323517
Phenotypes for gene: TMEM230 were set to Parkinson disease 21, MIM#616361
Review for gene: TMEM230 was set to AMBER
Added comment: A single family segregating a heterozygous missense (p.Arg141Leu) and supporting functional evidence. However, another group found a DNAJC13 variant in the same family also with supporting functional evidence. A stoploss was also identified in 9 Chinese Parkinson disease probands, however it was identified homozygous in 7 of these with no difference in the severity of phenotype. A similar stop loss was identified in a North American PD case. Another missense was identified in an apparently sporadic PD case (p.Tyr92Cys), but was also present in the unaffected mother (age 57 yrs). Another rare missense has been reported in a case with familial PD. The missense reported in a family from Southern Italy is too common in gnomAD v2.1 for a dominant disease (PMID: 31323517 - p.Ile125Met).
Sources: Expert list
Early-onset Parkinson disease v0.16 DNAJC13 Bryony Thompson edited their review of gene: DNAJC13: Changed phenotypes: Parkinson disease 21, MIM#616361
Early-onset Parkinson disease v0.16 DNAJC13 Bryony Thompson gene: DNAJC13 was added
gene: DNAJC13 was added to Early onset Parkinson disease. Sources: Expert list
Mode of inheritance for gene: DNAJC13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNAJC13 were set to 30788857; 24218364; 29309590; 31082451; 29887357; 27270108
Review for gene: DNAJC13 was set to AMBER
Added comment: A single family segregating a heterozygous missense (p.Asn855Ser) and supporting functional evidence. However, another group found a TMEM230 variant in the same family also with supporting functional evidence. Two missense reported in two other studies (PMID: 30788857 - p.Arg1382His; PMID: 29887357 - p.Arg903Lys) are more common in gnomAD v2.1 than would be expected for a dominant disorder.
Sources: Expert list
Early-onset Parkinson disease v0.15 DCAF17 Bryony Thompson Added comment: Comment on list classification: Dystonia rather parkinsonism appears to be a feature of this condition and this gene is one the dystonia panel.
Early-onset Parkinson disease v0.14 DCAF17 Bryony Thompson reviewed gene: DCAF17: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Woodhouse-Sakati syndrome MIM#241080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.12 CP Bryony Thompson reviewed gene: CP: Rating: GREEN; Mode of pathogenicity: None; Publications: 28012953; Phenotypes: Hemosiderosis, systemic, due to aceruloplasminemia MIM#604290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.12 CLN3 Bryony Thompson reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19489875, 11342698; Phenotypes: Ceroid lipofuscinosis, neuronal, 3 MIM#204200; Mode of inheritance: None
Early-onset Parkinson disease v0.12 CHCHD2 Bryony Thompson edited their review of gene: CHCHD2: Changed publications: 32068847, 25662902, 31600778, 26705026
Early-onset Parkinson disease v0.10 CHCHD2 Bryony Thompson gene: CHCHD2 was added
gene: CHCHD2 was added to Early onset Parkinson disease. Sources: Expert list
Mode of inheritance for gene: CHCHD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHCHD2 were set to 32068847; 25662902; 31600778
Phenotypes for gene: CHCHD2 were set to Parkinson disease 22, autosomal dominant MIM#616710
Review for gene: CHCHD2 was set to GREEN
Added comment: Five families with heterozygous variants, segregation evidence for T61I in multiple families. Supporting functional evidence suggesting mitochondrial dysfunction through the genes role in mitochondrial respiratory function.
Sources: Expert list
Early-onset Parkinson disease v0.9 C9orf72 Bryony Thompson Added comment: Comment on list classification: A repeat expansion is the cause of disease for this gene, which is currently not detectable by NGS.
Early-onset Parkinson disease v0.7 AFG3L2 Bryony Thompson reviewed gene: AFG3L2: Rating: RED; Mode of pathogenicity: None; Publications: 30252181; Phenotypes: optic atrophy, spastic ataxia, L-dopa-responsive parkinsonism; Mode of inheritance: Unknown
Early-onset Parkinson disease v0.7 PRKN Michelle Torres reviewed gene: PRKN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16476817, PMID: 14519684; Phenotypes: Parkinson disease, juvenile, type 2 600116 AR, Adenocarcinoma of lung, somatic 211980, Ovarian cancer, somatic 167000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.2 CP Zornitza Stark reviewed gene: CP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aceruloplasminaemia, MIM#604290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.1 PDE8B Zornitza Stark gene: PDE8B was added
gene: PDE8B was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review
Mode of inheritance for gene: PDE8B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PDE8B were set to 20085714; 26769607; 26475694
Phenotypes for gene: PDE8B were set to Striatal degeneration, autosomal dominant, MIM#609161
Review for gene: PDE8B was set to GREEN
Added comment: Movement disorder due to basal ganglia abnormalities, at least three families reported with heterozygous variants in this gene.
Sources: Expert Review
Early-onset Parkinson disease v0.0 XPR1 Zornitza Stark gene: XPR1 was added
gene: XPR1 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: XPR1 was set to Unknown
Early-onset Parkinson disease v0.0 WDR45 Zornitza Stark gene: WDR45 was added
gene: WDR45 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: WDR45 was set to Unknown
Early-onset Parkinson disease v0.0 VPS35 Zornitza Stark gene: VPS35 was added
gene: VPS35 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: VPS35 was set to Unknown
Early-onset Parkinson disease v0.0 VPS13A Zornitza Stark gene: VPS13A was added
gene: VPS13A was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: VPS13A was set to Unknown
Early-onset Parkinson disease v0.0 TWNK Zornitza Stark gene: TWNK was added
gene: TWNK was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: TWNK was set to Unknown
Early-onset Parkinson disease v0.0 TUBB4A Zornitza Stark gene: TUBB4A was added
gene: TUBB4A was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: TUBB4A was set to Unknown
Early-onset Parkinson disease v0.0 TH Zornitza Stark gene: TH was added
gene: TH was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: TH was set to Unknown
Early-onset Parkinson disease v0.0 TAF1 Zornitza Stark gene: TAF1 was added
gene: TAF1 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: TAF1 was set to Unknown
Early-onset Parkinson disease v0.0 SYNJ1 Zornitza Stark gene: SYNJ1 was added
gene: SYNJ1 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: SYNJ1 was set to Unknown
Early-onset Parkinson disease v0.0 SPR Zornitza Stark gene: SPR was added
gene: SPR was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: SPR was set to Unknown
Early-onset Parkinson disease v0.0 SPG11 Zornitza Stark gene: SPG11 was added
gene: SPG11 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: SPG11 was set to Unknown
Early-onset Parkinson disease v0.0 SNCA Zornitza Stark gene: SNCA was added
gene: SNCA was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: SNCA was set to Unknown
Early-onset Parkinson disease v0.0 SLC6A3 Zornitza Stark gene: SLC6A3 was added
gene: SLC6A3 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: SLC6A3 was set to Unknown
Early-onset Parkinson disease v0.0 SLC39A14 Zornitza Stark gene: SLC39A14 was added
gene: SLC39A14 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: SLC39A14 was set to Unknown
Early-onset Parkinson disease v0.0 SLC30A10 Zornitza Stark gene: SLC30A10 was added
gene: SLC30A10 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: SLC30A10 was set to Unknown
Early-onset Parkinson disease v0.0 SLC20A2 Zornitza Stark gene: SLC20A2 was added
gene: SLC20A2 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: SLC20A2 was set to Unknown
Early-onset Parkinson disease v0.0 RAB39B Zornitza Stark gene: RAB39B was added
gene: RAB39B was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: RAB39B was set to Unknown
Early-onset Parkinson disease v0.0 PTS Zornitza Stark gene: PTS was added
gene: PTS was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PTS was set to Unknown
Early-onset Parkinson disease v0.0 PSEN1 Zornitza Stark gene: PSEN1 was added
gene: PSEN1 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PSEN1 was set to Unknown
Early-onset Parkinson disease v0.0 PRNP Zornitza Stark gene: PRNP was added
gene: PRNP was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PRNP was set to Unknown
Early-onset Parkinson disease v0.0 PRKRA Zornitza Stark gene: PRKRA was added
gene: PRKRA was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PRKRA was set to Unknown
Early-onset Parkinson disease v0.0 PRKN Zornitza Stark gene: PRKN was added
gene: PRKN was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PRKN was set to Unknown
Early-onset Parkinson disease v0.0 POLG Zornitza Stark gene: POLG was added
gene: POLG was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: POLG was set to Unknown
Early-onset Parkinson disease v0.0 PLA2G6 Zornitza Stark gene: PLA2G6 was added
gene: PLA2G6 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PLA2G6 was set to Unknown
Early-onset Parkinson disease v0.0 PINK1 Zornitza Stark gene: PINK1 was added
gene: PINK1 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PINK1 was set to Unknown
Early-onset Parkinson disease v0.0 PDGFRB Zornitza Stark gene: PDGFRB was added
gene: PDGFRB was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PDGFRB was set to Unknown
Early-onset Parkinson disease v0.0 PDGFB Zornitza Stark gene: PDGFB was added
gene: PDGFB was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PDGFB was set to Unknown
Early-onset Parkinson disease v0.0 PARK7 Zornitza Stark gene: PARK7 was added
gene: PARK7 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PARK7 was set to Unknown
Early-onset Parkinson disease v0.0 PANK2 Zornitza Stark gene: PANK2 was added
gene: PANK2 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: PANK2 was set to Unknown
Early-onset Parkinson disease v0.0 OPA3 Zornitza Stark gene: OPA3 was added
gene: OPA3 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: OPA3 was set to Unknown
Early-onset Parkinson disease v0.0 MECP2 Zornitza Stark gene: MECP2 was added
gene: MECP2 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: MECP2 was set to Unknown
Early-onset Parkinson disease v0.0 MAPT Zornitza Stark gene: MAPT was added
gene: MAPT was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: MAPT was set to Unknown
Early-onset Parkinson disease v0.0 LYST Zornitza Stark gene: LYST was added
gene: LYST was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: LYST was set to Unknown
Early-onset Parkinson disease v0.0 LRRK2 Zornitza Stark gene: LRRK2 was added
gene: LRRK2 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: LRRK2 was set to Unknown
Early-onset Parkinson disease v0.0 KIF5A Zornitza Stark gene: KIF5A was added
gene: KIF5A was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: KIF5A was set to Unknown
Early-onset Parkinson disease v0.0 HTT Zornitza Stark gene: HTT was added
gene: HTT was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: HTT was set to Unknown
Early-onset Parkinson disease v0.0 GRN Zornitza Stark gene: GRN was added
gene: GRN was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: GRN was set to Unknown
Early-onset Parkinson disease v0.0 GCH1 Zornitza Stark gene: GCH1 was added
gene: GCH1 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: GCH1 was set to Unknown
Early-onset Parkinson disease v0.0 FTL Zornitza Stark gene: FTL was added
gene: FTL was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: FTL was set to Unknown
Early-onset Parkinson disease v0.0 FMR1 Zornitza Stark gene: FMR1 was added
gene: FMR1 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: FMR1 was set to Unknown
Early-onset Parkinson disease v0.0 FBXO7 Zornitza Stark gene: FBXO7 was added
gene: FBXO7 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: FBXO7 was set to Unknown
Early-onset Parkinson disease v0.0 DNAJC6 Zornitza Stark gene: DNAJC6 was added
gene: DNAJC6 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: DNAJC6 was set to Unknown
Early-onset Parkinson disease v0.0 DNAJC5 Zornitza Stark gene: DNAJC5 was added
gene: DNAJC5 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: DNAJC5 was set to Unknown
Early-onset Parkinson disease v0.0 DCTN1 Zornitza Stark gene: DCTN1 was added
gene: DCTN1 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: DCTN1 was set to Unknown
Early-onset Parkinson disease v0.0 DCAF17 Zornitza Stark gene: DCAF17 was added
gene: DCAF17 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: DCAF17 was set to Unknown
Early-onset Parkinson disease v0.0 CSF1R Zornitza Stark gene: CSF1R was added
gene: CSF1R was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: CSF1R was set to Unknown
Early-onset Parkinson disease v0.0 CP Zornitza Stark gene: CP was added
gene: CP was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: CP was set to Unknown
Early-onset Parkinson disease v0.0 COASY Zornitza Stark gene: COASY was added
gene: COASY was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: COASY was set to Unknown
Early-onset Parkinson disease v0.0 CLN3 Zornitza Stark gene: CLN3 was added
gene: CLN3 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: CLN3 was set to Unknown
Early-onset Parkinson disease v0.0 C9orf72 Zornitza Stark gene: C9orf72 was added
gene: C9orf72 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: C9orf72 was set to Unknown
Early-onset Parkinson disease v0.0 C19orf12 Zornitza Stark gene: C19orf12 was added
gene: C19orf12 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: C19orf12 was set to Unknown
Early-onset Parkinson disease v0.0 ATP1A3 Zornitza Stark gene: ATP1A3 was added
gene: ATP1A3 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: ATP1A3 was set to Unknown
Early-onset Parkinson disease v0.0 ATP13A2 Zornitza Stark gene: ATP13A2 was added
gene: ATP13A2 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: ATP13A2 was set to Unknown
Early-onset Parkinson disease v0.0 APP Zornitza Stark gene: APP was added
gene: APP was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: APP was set to Unknown
Early-onset Parkinson disease v0.0 AFG3L2 Zornitza Stark gene: AFG3L2 was added
gene: AFG3L2 was added to Early onset Parkinson disease_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship
Mode of inheritance for gene: AFG3L2 was set to Unknown