Variants in the SCN1A 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 the SCN1A 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 Dravet syndrome phenotype which is more severe than average. This first report of a de novo homozygous variant in the SCN1A gene, therefore, provides a clear illustration of a complex genotype—phenotype relationship.

SCN1A基因的变异已在具有广泛可变表型的癫痫患者中发现，它们通常是杂合的。在这里，我们报告了SCN1A基因中的一个纯合错义变体 NM_001165963.4：c.4319C>T (p.Ala1440Val)，它似乎与基因转换事件一起从头发生。这个变体很有可能，虽然位于蛋白质 Nav1.1 的关键功能域中，但取决于氨基酸取代的性质，可能不会导致蛋白质功能的完全丧失。并且在两个等位基因上都有这种变体的累积效应导致了比平均水平更严重的 Dravet 综合征表型。这是SCN1A从头 纯合变体的第一份报告 因此，基因清楚地说明了复杂的基因型-表型关系。