一个脊髓小脑共济失调3型家系的基因动态变异检测及分析  

Detection and analysis of dynamic variant in a pedigree affected with spinocerebellar ataxia type 3

作　　者：陈晨[1] 赵学潮 孔祥东[1] Chen Chen;Zhao Xuechao;Kong Xiangdong(Genetics and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450000,China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,450052

出　　处：《中华医学遗传学杂志》2020年第12期1364-1367,共4页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划 (2018YFC1002206-2)。

摘　　要：目的采用荧光引物PCR结合毛细管电泳的方法分析1个脊髓小脑共济失调(spinocerebellar ataxia,SCA)家系的基因变异情况,进行疾病分型,并提供遗传咨询。方法采集一个家系8名成员(含6例患者)的外周血样,提取基因组DNA。针对SCA常见亚型(SCA1、SCA2、SCA3、SCA6、SCA12和SCA17)设计6对荧光标记引物,并通过毛细管电泳筛选该家系的致病基因。结果先证者SCA3基因CAG动态变异的重复次数分别为8次和70次,超出正常重复范围(12~40次),确诊为SCA3型脊髓小脑共济失调患者。其他7名家系成员中5人SCA3基因CAG重复序列均检测到异常扩增,确诊为SCA3型患者,另有两人CAG重复序列未检测到异常扩增。结论SCA3基因CAG重复序列异常扩增是该家系的致病原因,通过荧光引物PCR结合毛细管电泳的方法可以快速准确地检出CAG重复序列动态变异所致的SCA患者。Objective To analyze the dynamic variant and clinical subtype of a pedigree affected with spinocerebellar ataxia(SCA)by using fluorescent-labeled primer combined with capillary electrophoresis.Methods Genomic DNA was extracted from 8 members including 6 patients and 2 healthy individuals from the pedigree.Six pairs of fluorescent-labeled primers were designed to screen pathological variants in association with common subtypes of SCA including SCA1,SCA2,SCA3,SCA6,SCA12 and SCA17.The PCR products were detected by capillary electrophoresis.Results The number of CAG repeats in the SCA3 gene of the proband were determined as 8 and 70,exceeded the normal range(12 to 40),which suggested a diagnosis of SCA3.The other five patients were all detected with abnormal CAG repeats in the SCA3 gene,while the two healthy individuals were determined to be within the normal range.Conclusion The abnormal expansion of CAG repeats in the SCA3 gene probably underlay the pathogenesis of the disease in this pedigree.Combined fluorescent-labeled primers PCR and capillary electrophoresis can detect dynamic variants among SCA patients with efficiency and accuracy.

关 键 词：脊髓小脑共济失调 毛细管电泳 CAG重复序列 基因检测 

分 类 号：R744.7[医药卫生—神经病学与精神病学]