脊髓小脑性共济失调一家系的遗传学研究

《脊髓小脑性共济失调一家系的遗传学研究》由会员上传分享，免费在线阅读，更多相关内容在行业资料-天天文库。

1、脊髓小脑性共济失调一家系的遗传学研究刘丹，郭洪，王凯，白云（400038重庆，第三军医大学基础部医学遗传学教研室）[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

2、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。[关键词]脊髓小脑性共济失调；动态突变；基因诊断[中图法分类号]R394.3[文献标志码]AGeneticanalysisofafamilywithspin

3、ocerebellarataxiaLiuDan，GuoHong，WangKai，BaiYun（DepartmentofMedicalGenetics,CollegeofBasicMedicalScience,ThirdMilitaryMedicalUniversity,Chongqing400038，China）[Abstract]ObjectiveTomakegeneticdiagnoseanddiscusstheclinicalcharacteristicsinanautosomaldomin

4、antinheritedfamilywithspinocerebellarataxias.MethodsFamilyinvestigationandpedigreeanalysiswereperformedinthisfamily,andtheCAGrepeatssizeofSCAcausativegeneweredetectedbycombiningpolymerasechainreaction(PCR)withdirectDNAsequencing.ResultsThisfamilywasch

5、aracterizedasanautosomaldominantinheritance.Theataxicsymptomssuchasgait,dysphagiaandslurredspeechinfamilypatientsweregraduallyappearedaftertheirthirty-yearold.Wetookgeneticdiagnoseforallfamilymembers,theresultsdemonstratedtheCAGrepeatsizesofSCA2andSCA

6、3causativegenewerenormalinallfamilymembersandcontrolpopulations,whereasinthreepatientsthesizeofSCA1mutatedallelewas43,48and50respectively.TheCAGrepeatsizesofmutatedalleleinanothertwofamilymemberswere53and50,sotheywerediagnosedaspresymptomaticSCA1patie

7、nts.ConclusionThefamilywasdiagnosedtospinocerebellarataxiatype1,whichwascausedbyCAGsequenceabnormalrepeated.WefoundtwopresymptomaticSCA1patientsaccordinggeneticdiagnose.[Keywords]spinocerebellarataxias；dynamicmutation；geneticdiagnoseCorrespondingautho

8、r:BaiYun,Tel:86-23-68752258,E-mail:baiyungene@gmail.com[通信作者]白云,电话：（023）68752258,E-mail:baiyungene@gmail.com4脊髓小脑性共济失调（spinocerebellarataxias，SCAs）旧称常染色体显性遗传性小脑性共济失调（autosomaldominantcerebellarataixas,ADCAs），是一种由遗传因素引起的神经系统退行性疾病，具有高度的临床和遗传异质性，