全基因组外显子测序联合连锁分析法进行家族性偏瘫性偏头痛致病基因CACNA1A新突变的研究  

A novel mutation in CACNA1A associated with familial hemiplegic migraine

作　　者：刘祥琴[1] 马勋泰 杜琼[1] 晏宁[3] 

机构地区：[1]四川省医学科学院四川省人民医院检验科,成都610071 [2]西南医科大学附属第一医院神经内科 [3]重庆医科大学附属大学城医院神经内科

出　　处：《中华检验医学杂志》2016年第9期705-709,共5页Chinese Journal of Laboratory Medicine

基　　金：重庆市自然科学基金（cstc2012jjA10093）;四川省人民医院青年基金项目（省医行[2014]94号）

摘　　要：目的：探索家族性偏瘫性偏头痛与CACNA1A基因突变的关系。方法通过收集2014年重庆医科大学附属大学城医院神经内科的一家族性偏瘫性偏头痛家系患者和正常人以及1000名正常对照DNA，对该家系的先证者和另一患者进行全基因组外显子测序，并进行连锁分析、CACNA1A基因测序验证研究和生物信息学分析。结果发现一个位于CACNA1A基因的8号外显子的新突变位点（c.1168A＞G），导致天冬酰胺替换为天冬氨酸（N390D）。结论 CACNA1A基因突变N390D是新发现的引起该家系家族性偏瘫性偏头痛的致病突变。Objective To identify mutations of CACNA1A gene in a family with hemiplegic migraine.Methods Total genomic DNA was extracted from a family with 3 affected members and 1 000 healthy controls.The proband and his patient sister were subjected to exome sequencing.Ten family members including 3 patients were subjected to linkage analysis.The coding exons of the CACNA1A gene were amplified and sequenced in affected and normal individuals. Bioinformatics analysis were performed.Results A novel CACNA1A mutation was identified in the 3 patients.The nonsense mutation of A to G was detected at nucleotide 1168 （ c.1168A 〉G） which converted the Asn codon （ AAT） to Asp （GAT） in exon 8.Conclusion The mutation（N390D） detected in the present study is considered to result in the Chinese Hemiplegic migraine family.

关 键 词：先兆偏头痛 钙通道 突变 误义 

分 类 号：R747.2[医药卫生—神经病学与精神病学]