De novo homozygous variant of the SCN1A gene in a patient with severe Dravet syndrome complicated by acute encephalopathy

AbstractVariants in theSCN1A gene have been identified in epilepsy patients with widely variable phenotypes and they are generally heterozygous. Here, we report a homozygous missense variant, NM_001165963.4: c.4319C>T (p.Ala1440Val), in theSCN1A gene which seemed to occur de novo together with a gene conversion event. It ’s highly possible that this variant, although located in a critical functional domain of protein Nav1.1, depending on the nature of the amino acid substitution, may not cause the complete loss of protein function. And the accumulated effect by having this variant on both alleles results in a Drav et syndrome phenotype which is more severe than average. This first report of a de novo homozygous variant in theSCN1A gene, therefore, provides a clear illustration of a complex genotype —phenotype relationship.

Source: Neurogenetics - March 5, 2021 Category: Genetics & Stem Cells Source Type: research