Abstract:

Objective　To study the clinical features and SCN1A gene mutation in a familial inherited Dravet syndrome family with dizygotic twins. Methods　The clinical manifestations of dizygotic twins with Dravet syndrome and GEFS + mother were summarized and SCN1A gene was sequenced. The relationship between genotype-phenotype of SCN1A gene and Dravet syndrome was analyzed by literature. Results　The dizygotic twins and their mother have de novo SCN1A gene mutant c.3624A＞T（p.R1208S） at the second loop of Na+ channel α subunit. This is very rare compared to the usual mutation domain at S4 or S5-S6. It is the first report in China that  Dravet syndrome dizygotic twins inherited SCN1A gene mutation from their mother who was diagnosed as GEFS+. Point mutations of SCN1A were more common，accounting for 93.8%. The relationships between phenotype-genotype were very complex，since other pathogenic factors may be involved in.  Conclusion　It is the first report in China that SCN1A gene mutation in a familial inherited Dravet syndrome with dizygotic twins and found a de novo SCN1A gene mutation of c.3624A＞T（p.R1208S），which is located at the very rare region of the protein.

Key words: inherited Dravet syndrome, familial Dravet syndrome, SCN1A, gene mutation, dizygotic twins

摘要：

目的    总结遗传性异卵双生Dravet综合征家系临床及SCN1A基因突变特点。方法　分析华中科技大学同济医学院附属同济医院2017年6月收治的异卵双生Dravet综合征患儿兄妹各1例和全身性热性惊厥附加症（GEFS+）母亲家系的临床特征，进行SCN1A基因测序。并结合文献分析基因突变类型与Dravet综合征的关系。结果　2例患儿及其母亲均携带未报道过的SCN1A基因突变c.3624A＞T（p.R1208S），该突变位于蛋白的罕见区域（Na+通道α亚基第2个环）。SCN1A基因突变以点突变多见，约占93.8%，突变位置与Dravet综合征临床表型的相关性复杂。结论　该病例为国内首次报道的遗传自双亲之一的异卵双生Dravet综合征。SCN1A基因突变c.3624A＞T （p.R1208S）发生于蛋白罕见区域，目前国际尚未报道。

关键词: 遗传性Dravet综合征, 家族性Dravet综合征, SCN1A, 基因突变, 异卵双生