脊髓小脑性共济失调一家系的遗传学研究  

Genetics of a Chinese family with spinocerebellar ataxia

作　　者：刘丹[1] 郭洪[1] 王凯[1] 白云[1] 

机构地区：[1]第三军医大学基础医学部医学遗传学教研室,重庆400038

出　　处：《第三军医大学学报》2011年第11期1152-1154,共3页Journal of Third Military Medical University

摘　　要：目的对一个常染色体显性遗传的脊髓小脑共济失调家系(spinocerebellar ataxias,SCA)进行基因诊断并探讨其临床特点。方法完成家系调查和系谱分析,通过聚合酶链式反应和直接测序的方法对收集到的家系成员进行脊髓小脑性共济失调致病基因CAG三核苷酸重复数目的检测。结果该家系呈常染色体显性遗传模式,家系中3名患者均于30岁后逐渐表现为行走不稳、饮水呛咳、言语不清等共济失调的临床特征。对所有家系成员进行基因诊断,结果发现,SCA2和SCA3致病基因的CAG重复数目均在正常范围内;而家系中3名患者SCA1致病基因出现异常等位基因,CAG扩增次数分别为43、48和51次,另有2名成员GAG重复次数分别为53次和50次,诊断为症状前患者。结论该家系为三核苷酸重复序列(CAG)动态突变引起的常染色体显性遗传脊髓小脑共济失调Ⅰ型,基因诊断还发现家系中2名症状前患者。Objective To do genetic diagnosis of an autosomal dominant spinocerebellar ataxia family and discuss its clinical characteristics.Methods Familial investigation and pedigree analysis were performed.The duplicate number of tri-nucleotides in pathogenic CAG was detected by polymerase chain reaction（PCR） and direct DNA sequencing in the family members.Results Autosomal dominant heredity was found in this family.Clinical symptoms such as gait,dysphagia and slurred speech occurred in three spinocerebellar ataxia patients of the family at the age of over 30 years.Genetic diagnosis of spinocerebellar ataxia showed that the CAG duplicate number of SCA2 and SCA3 was normal in all the family members of spinocerebellar ataxia patients,and abnormal allelic gene SCA1 was detected in 3 spinocerebellar ataxia patients.The CAG was amplified 43,48,and 51 times,respectively,and amplified 53 and 50 times for another 2 members of the family who were diagnosed as presymptomatic SCA1.Conclusion Type 1 spinocerebellar ataxia can be diagnosed in the family members of spinocerebellar ataxia patients according to their autosomal dominant heredity caused by dynamic mutations.Genetic diagnosis can be established in 2 presymptomatic SCA1 patients of the family.

关 键 词：脊髓小脑性共济失调 动态突变 基因诊断 

分 类 号：R394.3[医药卫生—医学遗传学] R596.102[医药卫生—基础医学]