中图分类号 R394. 3.docVIP

脊髓小脑性共济失调一家系的遗传学研究 刘丹1 郭洪1 王凯1 白云1 1第三军医大学基础部医学遗传学教研室，重庆，400038 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（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；而家系中三名患者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，另有两名成员 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CAG）动态突变引起的spinocerebellar ataxias，SCAs）；动态突变；基因诊断； 中图分类号：R394.3 Genetic Analysis of a Family with Spinocerebellar Ataxia LIU Dan1 GUO Hong1 WANG Kai1 BAI Yun1 1 Department of Medical Genetics, College of Basic Medical Science, Third Military Medical University, Chongqing 400038 China Abstract Objective To make genetic diagnose and discuss the clinical characteristics in an autosomal dominant inherited family with spinocerebellar ataxias. Methods Family investigation and pedigree analysis were performed in this family, and the CAG repeats size of SCA causative gene were detected by combining polymerase chain reaction (PCR) with direct DNA sequencing. Results This family was characterized as an autosomal dominant inheritance. The ataxic symptoms such as gait, dysphagia and slurred speech in family patients were gradually appeared after their thirty-year old. We took genetic diagnose for all family members, the results demonstrated the CAG repeat sizes of SCA2 and SCA3 causative gene were normal in all family members and control populations, whereas in three patients the size of SCA1 mutated allele was 43, 48 and 50 respectively. The CAG repeat sizes of mutated allele in another two family members were 53 and 50, so they were diagnosed as presymptomatic SCA1 patients. Conclusion The family was diagnosed to spinocerebellar ataxia type 1, which was caused by CAG sequence abnormal repeated. We found two presymptomatic SCA1 patients according genetic diagnose. Key words：Spinocerebellar Ataxias (SCAs), Dynamic Mutation, Genetic Diagnose Corresponding author: Bai Yun, Tel: +86-23-687522