散发性夜发额叶癫痫遗传学病因分析

Study in screening mutation in sporadic nocturnal frontal lobe epilepsy

目的研究中国夜发性额叶癫痫(nocturnal frontal lobe epilepsy,NFLE)散发患者遗传学病因,探讨烟碱乙酰胆碱受体(nicotinic acetylcholine receptor,nAChR)相关基因在NFLE发病机制中的作用。方法经临床资料、家族史及辅助检查综合诊断,收集77例中国非家族性NFLE患者,提取基因组DNA,聚合酶链反应扩增nAChR相关基因CHRNA4、CHRNB2及CHRNA2部分区域,确认是否存在突变。如存在突变,则进一步分析突变对蛋白质疏水性和二级结构造成的影响。结果发现1例6岁患儿存在1种CHRNA4的新型杂合错义突变,导致nAChR-α4亚单位第3、4跨膜区间胞内环405位的丝氨酸突变为苯丙氨酸(S405F)。在200例中国人群健康对照筛查中未见同样突变。突变对蛋白质疏水性及二级结构均有一定影响。结论中国人群散发NFLE病例中存在CHRNA4基因的S405F突变,可能是NFLE新型遗传学病因。

Objective To analyze the genetic feature of Chinese sporadic nocturnal frontal lobe epilepsy（NFLE） and assess the role of the mutations of nicotinic acetylcholine receptor（nAChR）.Methods We recruited 77 Chinese patients diagnozed as sporadic NFLE based on case history,family history,designed mutation screening of CHRNA4,CHRNB2 and CHRNA2.After the mutation was identified,the protein hydrophobicity and secondary structures were analyzed.Results We found a missense mutation in CHRNA4 in a 6 years old male NFLE patient.The mutation caused a Ser-to-Phe substitution at amino acid position 405 in the M3-M4 intracellular loop and changed the protein hydrophobicity and secondary structures.The mutation was absent in 200 healthy control individuals.Conclusion The missense mutation S405F of CHRNA4 in Chinese sporadic NFLE patient may be a genetic etiology in the pathogenesis of sporadic NFLE.