SACS基因复合杂合突变导致Charlevoix-Saguenay型痉挛性共济失调一家系两例  

Identification of compound heterozygous mutations of SACS gene in two patients from a pedigree with spastic ataxia of Charlevoix-Saguenay

作　　者：李世容 陈永平[1] 袁晓琴[1] 魏倩倩[1] 欧汝威[1] 顾孝静 商慧芳 Li Shirong , Chen Yongping , Yuan Xiaoqin , Wei Qianqian, Ou Ruwei , Gu Xiaojing , Shang Hui fang(Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China ; Department of Neurology, Guizhou Provincial People＇s Hospital, Guiyang , Guizhou 550002, China)

机构地区：[1]四川大学华西医院神经内科,成都610041 [2]贵州省人民医院神经内科,贵阳550002

出　　处：《中华医学遗传学杂志》2018年第4期507-510,共4页Chinese Journal of Medical Genetics

基　　金：贵阳市科技计划项目（[20151001]71）;贵州省科技计划合作项目（[2015]7150）;贵州省科技计划项目（[2017]5631）;国家重点研发计划精准医学研究重点专项（2016YFC0901504）

摘　　要：目的对1个常染色体隐性遗传痉挛性共济失调Charlevoix-Saguenay型（autosomal recessive spastic ataxia of Charlevoix-Saguenay, ARSACS）家系进行SACS基因突变分析，探讨其遗传学病因。方法应用目标区捕获高通量靶向测序对SACS基因进行突变筛查，用Sanger测序对突变位点进行验证。结果测序结果显示先证者和弟弟存在SACS基因C．13085T〉G（P．14362R）和C．5236dupA（P．T1746fs）复合杂合突变，父亲携带SACS基因c．5236dupA（P．T1746fs）杂合突变，母亲携带SACS基因C．13085T〉G（p．14362R）杂合突变，因此患者的C．5236dupA（P．T1746fs）和C．13085T〉G（P．14362R）突变分别来自父母。经检索人类基因突变数据库这两个变异均为未报道过的新突变，根据美国医学遗传学及基因组学会遗传变异解读指南，提示均为可能的致病性突变。结论C．5236dupA（P．T1746fs）和C．13085T〉G（P．14362R）突变为该ARSACS家系患者的遗传学病因，新突变的检出丰富了SACS基因突变谱。Objective To detect potential mutations of the spastic ataxia of Charlevoix-Saguenay （SACS） gene in a pedigree affected with autosomal recessive spastic ataxia of Charlevoix-Saguenay （ARSACS）. Methods Genomic DNA was extracted from peripheral blood samples of the proband and her family members. All exons and flanking sequences of the SACS gene were analyzed by high-throughput sequencing. Suspected mutations were verified with Sanger sequencing. Results Next generation sequencing revealed novel compound heterozygous mutations of the SACS gene, namely c. 13085T〉G （p. I4362R） and c. 5236dupA （p. T1746fs）, in the proband, which were respectively derived from her parents. The mutations were confirmed by Sanger sequencing. Conclusion The c. 5236dupA （p. T1746fs） and c. 13085 T〉G （p. I4362R） mutations of the SACS gene probably underlie the ocular symptoms and hearing loss in the proband.

关 键 词：Charlevoix-Saguenay型痉挛性共济失调 SACS基因 基因突变 

分 类 号：R440[医药卫生—诊断学] R744.7[医药卫生—临床医学]