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| Genetic Epilepsy v0.2060 | NALCN |
Rylee Peters gene: NALCN was added gene: NALCN was added to Genetic Epilepsy. Sources: Literature Mode of inheritance for gene: NALCN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NALCN were set to 30167850 Phenotypes for gene: NALCN were set to Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (MIM#615419) Review for gene: NALCN was set to GREEN Added comment: PMID: 30167850 – Cohort of individuals with novel NALCN or UNC80 variants; includes 16 individuals with biallelic NALCN variants and 1 individual with a de novo NALCN variant. - All individuals (16/16) with biallelic NALCN variants presented with neonatal hypotonia, failure to thrive, ID, and muscular hypotonia. Other clinical features include severe ID (14/16), nonverbal (14/16), non-walking (13/16), chronic constipation (14/16), extrapyramidal/abnormal movements (12/16), strabismus (12/16), sleeping difficulties (10/16), increased tendency to infections (9/16), and some individuals presented with seizures (7/16). - Table 1 describes clinical features of individuals with biallelic NALCN variants, showing 13/19 previously published individuals also had seizures. Sources: Literature |
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| Genetic Epilepsy v0.1851 | UNC79 |
Krithika Murali gene: UNC79 was added gene: UNC79 was added to Genetic Epilepsy. Sources: Literature Mode of inheritance for gene: UNC79 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UNC79 were set to PMID:37183800 Phenotypes for gene: UNC79 were set to Complex neurodevelopmental disorder - MONDO:0100038 Review for gene: UNC79 was set to AMBER Added comment: PMID:37183800 Bayat et al 2023 report 6 unrelated patients with heterozygous NMD-predicted LoF variants in UNC79 - x1 canonical splice site variant, x5 nonsense/frameshift. 5 were confirmed de novo, 1 not identified in mother - father unavailable for testing. All variants absent in gnomAD and v2 pLI score for UNC79 is 1. Patients with UNC79 variants were identified through GeneMatcher or an international network of Epilepsy and Genetics departments. x1 patient underwent duo exome sequencing, remaining had trio exome sequencing - no other causative variants identified. Phenotypic features included: - 4/6 autistic features - 5/6 patients mild-moderate ID - 4/6 behavioural issues (aggression, stereotypies) - 4/6 epilepsy (focal to bilateral tonic-clonic seizures) - 5/6 hypotonia unc79 knockdown drosophila flies exhibited significantly higher rate of seizure-like behaviour than controls. unc79 haploinsufficiency shown to lead to significant reduction in protein levels of both unc79 and unc80 in mouse brains anddeficiency in hippocampal-dependent learning and memory in mice. Authors have reviewed their own evidence in relation to the gene-disease criteria detailed by Strande et al 2017 and note that their clinical and experimental data provides moderate-level evidence supporting the association between UNC79 and a neurodevelopment disorder including ASD. Evidence emerging is promising, however Amber association favoured due to clinical phenotypic range reported between affected individuals and their lack of specificity. Sources: Literature |
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| Genetic Epilepsy v0.898 | UNC80 | Zornitza Stark Marked gene: UNC80 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.898 | UNC80 | Zornitza Stark Gene: unc80 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.898 | UNC80 | Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.897 | UNC80 | Zornitza Stark Publications for gene: UNC80 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.896 | UNC80 | Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.895 | UNC80 |
Zornitza Stark commented on gene: UNC80: UNC80 is part of the NALCN complex, and this is considered a NALCN channelopathy. More than 20 individuals from more than 5 unrelated families reported with bi-allelic variants in this gene and severe autosomal recessive neurodevelopmental disorder with onset at birth or in early infancy. Affected individuals show severe global developmental delay with poor or absent speech and absent or limited ability to walk. Some have had seizures; brain structure is typically normal. UNC80 knockout mice are neonatal lethal. |
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| Genetic Epilepsy v0.895 | UNC80 | Zornitza Stark reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: 26708751, 26708753, 26545877, 32620897, 30167850, 30167850; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.0 | UNC80 |
Zornitza Stark gene: UNC80 was added gene: UNC80 was added to Genetic Epilepsy_AustralianGenomics_VCGS. Sources: Australian Genomics Health Alliance Epilepsy Flagship,Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: UNC80 was set to Unknown |
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