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SCN1A has been implicated in a small number of sporadic myoclonic-astatic epilepsy (Doose syndrome) cases but overall evidence for a causal role is sparse. A de novo heterozygous missense variant c.3521C>G (p.Thr1174Ser) was reported in a single patient with MAE (PMID:15944908). However, analysis of 22 unrelated sporadic MAE cases failed to identify pathogenic SCN1A mutations, arguing against a frequent contribution to MAE (PMID:14642997). No familial segregation has been observed, and functional studies have not evaluated MAE-specific SCN1A variants directly, although SCN1A haploinsufficiency is established in related epilepsies. This conflicting dataset supports a Limited gene–disease association, with insufficient genetic and experimental evidence for routine diagnostic use. Further large-scale screening and functional characterization in MAE are required.
Gene–Disease AssociationLimitedSingle proband with de novo SCN1A missense variant; negative screening of 22 sporadic MAE cases; no segregation support Genetic EvidenceLimitedOnly one de novo variant reported in MAE; lack of family segregation and low case count Functional EvidenceLimitedNo direct functional studies on MAE-specific SCN1A variants; mechanism inferred from related epilepsies |