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| Intellectual disability syndromic and non-syndromic v0.5192 | TAB2 |
Lucy Spencer gene: TAB2 was added gene: TAB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: TAB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TAB2 were set to 35971781 Phenotypes for gene: TAB2 were set to Congenital heart defects, multiple types, 2 MONDO:0014000 Review for gene: TAB2 was set to GREEN Added comment: PMID: 35971781 - expansion of the phenotype, 14 patients with TAB2 variants 6 have dev delay and 4 are also listed as having ID along with other phenotype features associated with this gene. Note- there is a previous review of this paper in the mendeilome as amber Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.4706 | ENTPD1 |
Zornitza Stark gene: ENTPD1 was added gene: ENTPD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: ENTPD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ENTPD1 were set to 35471564 Phenotypes for gene: ENTPD1 were set to Spastic paraplegia 64, autosomal recessive, MIM# 615683 Review for gene: ENTPD1 was set to GREEN Added comment: 27 individuals from 17 families published, expanding the phenotype to a complex neurodevelopmental disorder characterised by ID, white matter abnormalities and spastic paraplegia. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.4244 | NUP85 |
Zornitza Stark gene: NUP85 was added gene: NUP85 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP85 were set to 34170319; 30179222 Phenotypes for gene: NUP85 were set to Intellectual disability Review for gene: NUP85 was set to AMBER Added comment: Bi-allelic variants in this gene are associated with nephrotic syndrome in 3 families. Phenotype expansion: PMID: 34170319 - Ravindran et al 2021 report two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS. In the first family, a 9 yo female, with consanguineous parents, is reported to have a missense variant in NUP85 (c.932G > A; p.R311Q). Intrauterine growth restriction was noticed. At birth microcephaly was observed (OFC < 3rd centile, < −3.6 SD) as well as hypotrophy [weight −2.8 SD), length 45 cm (−2.7 SD), both <3rd centile], facial dysmorphism, syndactyly, long and thin fingers, and bilateral pes adductus. She has severe developmental delay with strongly delayed motor milestones and absent speech. Drug-resistant, genetic epilepsy with focal-onset seizures started in the first year of life. She had no clinical, laboratory or radiological findings indicative of kidney dysfunction. In the second family, compound heterozygous missense variants in NUP85 were detected (c.1109A > G, c.1589 T > C;p.N370S, p.M530T ) in a fetus. MRI of the fetal brain at 24 + 2 GW indicated complete agenesis of the corpus callosum, abnormal sulcation in the left frontal lobe, nodularity of the frontal horn and trigone with focal puckering of the left lateral ventricle. PMID: 30179222 - Braun et al 2018 - 2 individuals from 1 of the families reported with steroid-resistant nephrotic syndrome were also reported to have intellectual disability but showed no structural brain defects. The degree of intellectual disability is not stated. They were found to have 2 compound heterozygous alleles (c.405+1G>A and c.1741G>C, p.Ala581Pro) in NUP85. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.3921 | SAMD9L |
Paul De Fazio gene: SAMD9L was added gene: SAMD9L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: SAMD9L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SAMD9L were set to Intellectual disability Review for gene: SAMD9L was set to RED gene: SAMD9L was marked as current diagnostic Added comment: Missense variant reported de novo in a patient with moderate ID, in a large cohort study. Author described it as a phenotype expansion as ataxia-pancytopenia not found in that patient. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.3272 | DIP2B | Bryony Thompson Added comment: Comment on list classification: Only repeat expansion reported. Added as an STR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3270 | FRA12A |
Bryony Thompson STR: FRA12A was added STR: FRA12A was added to Intellectual disability syndromic and non-syndromic. Sources: Other 5'UTR tags were added to STR: FRA12A. Mode of inheritance for STR: FRA12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: FRA12A were set to 17236128 Phenotypes for STR: FRA12A were set to Mental retardation, FRA12A type MIM#136630 Review for STR: FRA12A was set to AMBER Added comment: NM_173602.2:c.-137CGG[X] All individuals expressing FRA12A had CGG-repeat expansion. The length of the expanded allele in 3 unaffected FRA12A carriers was 650–850 bp. In the two affected patients from 2 families with FRA12A, the length of the expanded allele was ∼1,050-1,150 bp. 70 controls used to determine the "normal" repeat range. Sources: Other |
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| Intellectual disability syndromic and non-syndromic v0.2920 | CTNND1 |
Zornitza Stark gene: CTNND1 was added gene: CTNND1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: CTNND1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CTNND1 were set to 28301459; 32196547 Phenotypes for gene: CTNND1 were set to Blepharocheilodontic syndrome 2, MIM# 617681 Review for gene: CTNND1 was set to AMBER Added comment: 4 individuals from 3 unrelated families with blepharocheilodontic syndrome and mutations in the CTNND1 gene reported originally in PMID 28301459. All had eyelid anomalies, including ectropion of the lower lids, euryblepharon, lagophthalmia, and distichiasis. In addition, all 4 showed typical facial dysmorphism with hypertelorism, flat face, and high forehead, and all had conical teeth and tooth agenesis. Three had cleft lip and palate, 3 had hair anomalies, and 1 had hypothyroidism due to hypoplasia or aplasia of the thyroid gland. None of the patients exhibited anal atresia or neural tube defects. PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. 8/13 patients showed cleft palate. Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13). This more recent publication suggests a broader phenotype associated with CTNND1 variants including dev delay, ADHD/ASD, behavioural issues. Unclear from description whether significant ID present. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.2750 | EXOC2 |
Konstantinos Varvagiannis gene: EXOC2 was added gene: EXOC2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC2 were set to 32639540 Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology Penetrance for gene: EXOC2 were set to Complete Review for gene: EXOC2 was set to AMBER Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants). Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.2362 | XPA | Zornitza Stark Publications for gene: XPA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.2361 | XPA | Zornitza Stark reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 26302748, 25566891, 24135642; Phenotypes: Xeroderma pigmentosum, group A, OMIM# 278700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.1545 | XPA | Zornitza Stark Marked gene: XPA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.1545 | XPA | Zornitza Stark Gene: xpa has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.1463 | GLS |
Zornitza Stark gene: GLS was added gene: GLS was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GLS were set to 30970188 Phenotypes for gene: GLS were set to Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412 Review for gene: GLS was set to AMBER Added comment: Three unrelated individuals described with compound het variants, however, note one of these is a triplet expansion in the 5' UTR, this may not be tractable depending on sequencing modality. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.1341 | LSS |
Chirag Patel gene: LSS was added gene: LSS was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSS were set to PMID: 30723320 Phenotypes for gene: LSS were set to Cataract 44, OMIM #616509; Hypotrichosis 14, OMIM #618275 Review for gene: LSS was set to GREEN Added comment: Expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. Ten APMR individuals from 6 unrelated families with biallelic variants in LSS. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.313 | XPA |
Chirag Patel Source Genetic Health Queensland was removed from XPA. Source Expert list was added to XPA. Mode of inheritance for gene XPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: XPA were changed from to Xeroderma pigmentosum, group A; OMIM# 278700 |
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| Intellectual disability syndromic and non-syndromic v0.312 | XPA | Chirag Patel reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, group A, OMIM# 278700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.0 | XPA |
Zornitza Stark gene: XPA was added gene: XPA was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: XPA was set to Unknown |
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