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| Mendeliome v1.513 | GABRA3 | Zornitza Stark Marked gene: GABRA3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.513 | GABRA3 | Zornitza Stark Gene: gabra3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.513 | GABRA3 | Zornitza Stark Phenotypes for gene: GABRA3 were changed from Epilepsy, intellectual disability, dysmorphic features, to Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features, MIM# 301091 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.512 | GABRA3 | Zornitza Stark Classified gene: GABRA3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.512 | GABRA3 | Zornitza Stark Gene: gabra3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.507 | GABRA3 |
Sarah Pantaleo gene: GABRA3 was added gene: GABRA3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GABRA3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: GABRA3 were set to PMID: 29053855 Phenotypes for gene: GABRA3 were set to Epilepsy, intellectual disability, dysmorphic features, Penetrance for gene: GABRA3 were set to Incomplete Review for gene: GABRA3 was set to GREEN Added comment: Six variants in GABRA3 encoding the alpha3-subunit of the GABA(A) receptor. Five missense variants and one micro duplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus. The variants co-segregated mostly but not completely with the phenotype in the families, indicating in some cases incomplete penetrance, involvement of other genes, or presence of phenocopies. Overall, males were more severely affected and there were three asymptomatic female mutation carriers compared to only one male without a clinical phenotype. Mechanism suggested - three detected missense variants are localised in the extracellular GABA-binding NH2-terminus, one in the M2-M3 linker and one in the M4 transmembrane segment of the alpha3-subunit. Functional studies in Xenopus leaves oocytes revealed a variable but significant reduction of GABA-evoked anion currents for all mutants compared to wild-type receptors. The degree of current reduction correlated partially with the phenotype. Results reveal that rare loss-of-function variants in GABRA3 increase the risk for a varying combination of epilepsy, intellectual disability/developmental delay and dysmorphic features, presenting in some pedigrees with an X-linked inheritance pattern. Sources: Literature |
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