Arina Puzriakova Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY; Rett-like phenotype to Cornelia de Lange syndrome 2, OMIM:300590; Cornelia de Lange syndrome 2, MONDO:0010370; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044; Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771
Rebecca Foulger edited their review of gene: SMC1A: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER
Tracy Lester reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: ; Publications: 28166369; Phenotypes: Cornelia de Lange syndrome 2, 300590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rebecca Foulger Added comment: Comment on mode of inheritance: Set MOI to X-linked dominant to match Gene2Phenotype and the MOI for SMC1A on the Intellectual disability panel. So far, mostly females have gross gene alterations of SMC1A, which are likely not tolerated in males (PMID:19842212).
Rebecca Foulger Mode of inheritance for gene: SMC1A was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green based on external review by Deb Pal, and a literature review. Plenty of recent papers reporting SMC1A variants causing epilepsy in female patients (e.g. PMIDs:31098032, 28677859, 28166369, 26752331,26386245,26358754). SMC1A variants can cause Cornelia de Lange syndrome (CdLS) but can also cause ID and epilepsy in the absence of CdLS features (PMID:31185419). Plus 'confirmed' rating in Gene2Phenotype for EPILEPTIC ENCEPHALOPATHY.
Rebecca Foulger Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY to Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY; Rett-like phenotype
Rebecca Foulger Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2 300590 to Cornelia de Lange syndrome 2, 300590; seizures; EPILEPTIC ENCEPHALOPATHY
Rebecca Foulger changed review comment from: PMID:31185419: Oguni et al 2019 report a missense variant (c.2683C>G:pArg895Gly) of SMC1A affecting a daughter (proband) and her mother. The daughter began having epileptic seizures age 2 years 1 month, progressing into cluster seizures. The mother began to have cluter seizures age 12 and had moderate ID. Neither individual had typical CdLS morphological features. Sequencing confirmed the variant was present in daughter and mother, but not other maternal family members. Blood samples from the paternal side were unavailable.; to: PMID:31185419: Oguni et al 2019 report a missense variant (c.2683C>G:pArg895Gly) of SMC1A affecting a daughter (proband) and her mother. The daughter began having epileptic seizures age 2 years 1 month, progressing into cluster seizures. The mother began to have cluster seizures age 12 and had moderate ID. Neither individual had typical CdLS morphological features. Sequencing confirmed the variant was present in daughter and mother, but not other maternal family members. Blood samples from the paternal side were unavailable.
Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported four unrelated cases in which seizures are a phenotypic feature.
Sarah Leigh Mode of inheritance for gene: SMC1A was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)