Q1OR mutation in SCN9A gene is associated with generalized epilepsy with febrile seizures plus
Q1OR mutation in SCN9A gene is associated with generalized epilepsy with febrile seizures plus
复制标题
SCN9A 基因 Q1OR 突变与全身性癫痫伴热性惊厥相关
DOI：
10.1016/j.seizure.2017.06.023
复制
发表时间：
2017-08-01
影响因子：
3
通讯作者：
Feng, Jianhua
中科院分区：
文献类型：
--
作者：
Cen, Zhidong;Lou, Yuting;Feng, Jianhua
2.临床异质性在遗传性疾病中很常见。即使是具有相同SCN 1A突变的GEFS+家系中的受影响成员也可能表现出从热性惊厥到Dravet综合征（一种严重的癫痫性脑病）的不同表型。SCN9A在人类中的相关表型多种多样，包括IEM、PEPD、SFN和CIP。SCN 9A编码Na V 1.7，其主要在背根神经节的神经元中表达，并且已初步分类为外周神经系统通道。然而，也报道了Na V 1.7在脑（胚胎海马神经元）中的表达，并表明其在中枢神经系统中的作用[4]。报告了一个经证实的GEFS+大家系和几例与SCN 9A突变相关的热性惊厥散发患者，这支持癫痫发作疾病是SCN 9A的第五种表型。然而，关于SCN9A在癫痫发作中的作用的报道并不多见，且仍存在争议。Singh等人认为，SCN9A是SCN1A突变患者Dravet综合征的潜在修饰基因[1]。Mulley等人发现，在Dravet综合征中，SCN9A的罕见变体显著富集，但Dravet综合征患者和正常对照之间的破坏性变体相似，这支持SCN9A在Dravet综合征遗传易感性中的作用[2]。
2. DiscussionClinical heterogeneity is common in genetic diseases. Even affected members in a GEFS+ pedigree with the same SCN1A mutation could present different phenotypes from febrile seizures to Dravet syndrome, a severe epileptic encephalopathy. SCN9A associated phenotypes in human were varied and included IEM, PEPD, SFN and CIP. SCN9A encodes Na V 1.7, which is mainly expressed in neurons of the dorsal root ganglia and has preliminarily been classified as a peripheral nervous system channel. However, expression of Na V 1.7 in brain (embryonic hippocampal neurons) was also reported and suggested a role in the central nervous system [4]. A confirmed large pedigree of GEFS+ and several sporadic patients with febrile seizures associated with mutations in SCN9A were reported, which supported seizure disorders as a fifth phenotype of SCN9A. However, the reports about the role of SCN9A in seizure disorders were rare and still debating. Singh et al. suggested SCN9A as a potential modifier gene to Dravet syndrome in patients with SCN1A mutations [1]. Mulley et al. found that rare variants in SCN9A were significantly enriched in Dravet syndrome, but damaging variants were similar between Dravet syndrome patients and normal controls, which supported a role for SCN9A in genetic susceptibility to Dravet syndrome [2].