一例巨轴索神经病患者中发现GAN基因两种新型致病突变  

Two novel pathogenic mutations of GAN gene identified in a patient with giant axonai neuropathy

作　　者：王娟[1] 马晴雯[1] 蔡勤[1] 刘艳娜 王伟[1] 任兆瑞[1] 

机构地区：[1]上海市儿童医院上海交通大学附属儿童医院上海医学遗传研究所,卫生部医学胚胎分子生物学重点实验室暨上海市胚胎与生殖工程重点实验室,200040

出　　处：《中华医学遗传学杂志》2016年第3期292-295,共4页Chinese Journal of Medical Genetics

基　　金：国家科技支撑计划（2012BA109804）;上海市卫生系统重要疾病联合攻关项目（2013ZYJB0015）

摘　　要：目的寻找1例疑似巨轴索神经病患者的致病突变位点，为疾病诊断提供科学资料。方法应用目标序列捕获测序技术对患者进行遗传筛查，找到巨轴突蛋白基因（Gigaxonin，GAIN）的可疑致病突变位点，并提取患者父母的外周血DNA，进行Sanger测序验证。同时对200名正常人的400个GAN基因进行Sanger测序。此外，应用生物信息学软件Polyphen对突变巨轴突蛋白进行了功能预测。结果在患者GAN基因中鉴定出2种新型突变：c．778G〉T（p．Glu260Ter）和c．277G〉A（p．Gly93Arg），为复合杂合突变；Sanger测序证实c．778G〉T（p．Glu260Ter）突变源于父方，c．277G〉A（P．Gly93Arg）突变则与母亲相同。在200名正常人GAN基因中未检测到同样的突变，排除其为多态性。生物信息学分析预测这两种新型GAN突变均可引发巨轴突蛋白功能异常。结论研究鉴定出了患者GAN的两种新型突变，它们均可能引起巨轴突蛋白结构和功能的异常，从而导致疾病的发生，为日后类似疾病的诊断提供了依据。Objective To explore the disease-causing mutations in a patient suspected for giant axonal neuropathy （GAN）. Methods Target sequence capture sequencing was used to screen potential mutations in genomic DNA extracted from peripheral blood sample of the patient. Sanger sequencing was applied to confirm the detected mutation. The mutation was verified among 400 GAN alleles from 200 healthy individuals by Sanger sequencing. The function of the mutations was predicted by bioinformatics analysis. Results The patient was identified as a compound heterozygote carrying two novel pathogenic GAN mutations, i. e. , c. 778G〉T （p. Glu260Ter） and c. 277G〉A （p. Gly93Arg）. Sanger sequencing confirmed that the c. 778G〉T （p. Glu260Ter） mutation was inherited from his father, while c. 277G〉A （p. Gly93Arg） was inherited from his mother. The same mutations was not found in the 200 healthy individuals. Bioinformatics analysis predicted that the two mutations probably caused functional abnormality of gigaxonin. Conclusion Two novel GAN mutations were detected in a patient with GAN. Both mutations are pathogenic and can cause abnormalities of gigaxonin structure and function, leading to pathogenesis of GAN. The results may also offer valuable information for similar diseases.

关 键 词：巨轴索神经病 GAN基因突变 目标序列捕获测序 

分 类 号：R748[医药卫生—神经病学与精神病学]