Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
Neurosci Lett. 2011 Sep 26;503(1):27-30. doi: 10.1016/j.neulet.2011.08.001. Epub 2011 Aug 6.
Generalized epilepsy with febrile seizures plus (GEFS(+)) is a common familial epilepsy syndrome, which generally develops in childhood. GEFS(+) is caused by mutations in the sodium-channel α1-subunit (SCN1A). In this report, we investigated a Chinese family with an autosomal dominant form of GEFS(+). The affected GEFS(+) patients in this family displayed significant inter-family clinical heterogeneity. Linkage analysis localized the disease-causing gene to chromosome 2q24, where SCN1A is located. Furthermore, DNA sequencing of the whole coding region of SCN1A revealed a novel heterozygous nucleotide substitution (c.577C>T) causing a missense mutation (p.L193F) in the S3 segment of SCN1A domain D1. Our results expand the spectrum of SCN1A mutations and provide novel insights between the SCN1A mutations and the clinical variations of GEFS(+).
热性惊厥附加症（GEFS(+))是一种常见的家族性癫痫综合征，通常在儿童时期发病。GEFS(+)是由钠通道α1亚基（SCN1A）基因突变引起的。本研究报道了一个具有常染色体显性遗传方式的 GEFS(+)中国家系。该家系中受累的 GEFS(+)患者表现出明显的家族间临床异质性。连锁分析将致病基因定位于 SCN1A 所在的 2q24 染色体上。此外，对 SCN1A 全长编码区的 DNA 测序发现一个新的杂合核苷酸替换（c.577C>T），导致 SCN1A 域 D1 的 S3 片段上出现一个错义突变（p.L193F）。我们的研究结果扩展了 SCN1A 突变谱，并为 SCN1A 突变与 GEFS(+)的临床变异之间提供了新的见解。
