云南地区脊髓小脑共济失调临床特征和基因突变分析  

Clinical features and genetic mutation analysis of spinocerebellar ataxias in Yunnan region

作　　者：李海江[1] 张林明[1] 陈涛[1] 杨丹[1] 宋建平[1] 王丽红[1] 朱杨帆 

机构地区：[1]昆明医科大学第一附属医院神经内科,650032

出　　处：《中华神经科杂志》2015年第6期503-508,共6页Chinese Journal of Neurology

基　　金：云南省应用基础研究计划项目（2011FB178）

摘　　要：目的 确定云南地区脊髓小脑共济失调（spinocerebellar ataxias,SCAs）家系的临床特征和基因分型.方法 选择2011年1月至2014年7月昆明医科大学第一附属医院神经内科收集的14个SCAs家系,共183份家系成员血液标本,应用PCR扩增、琼脂糖凝胶电泳、DNA测序等方法确定先证者的基因型,开展症状前检测,分析患者的临床特征.结果 14个SCAs家系中有9个为SCA3型,1个为SCA2型,4个SCAs家系未能进行基因分型.1例SCA3患者CAG重复数为46/77次,为双等位基因纯合突变,该患者起病早,病情重,进展快.发现1例SCA3伴多囊肾病家系,其先证者SCA3基因CAG重复次数为28/76,1个等位基因的重复次数在全突变范围,其多囊肾病1基因外显子23发生错义突变.结论 云南地区汉族人群以SCA3型最常见,存在15/46次前突变及46/77次双等位基因纯合突变,纯合突变有加重患者病情、加速病程进展的可能.SCA3与多囊肾病发生于同一家系实属罕见,提示两致病基因之间可能存在交互作用.Objective To identify the specific genotype and analyze clinical features of spinocerebellar ataxias （SCAs） pedigree in the region of Yunnan Province.Methods Fourteen SCAs pedigrees and 183 blood samples of the family members were collected between January 2011 and July 2014 from Department of Neurology,First Affiliated Hospital of Kunming Medical College.Polymerase chain reaction （PCR） amplification,agarose gel electrophoresis and DNA sequencing technologies were utilized to identify the specific genotype of SCAs pedigree.Presymptomatic tests were carried out and the clinical features and genetic test results of patients were carefully analyzed.Results SCA3 was the most common subtype of SCAs in the Han nationality of Yunnan region.Nine of the 14 families were SCA3,only one family was SCA2.Additionally,there were four SCAs families that remained indeterminate.The patients with di-allele mutations （46/77） of SCA3 gene had early onset,rapid progression and serious clinical symptoms.Hereditary SCA3 and autonomic dominant polycystic kidney disease can happen simultaneously in a family.The proband SCA3 gene＇ s CAG repeat number is 28/76,and repetitions of the mutation allele are in all range.The PKD1 gene exon 23 is found to be in abnormal sequence.Conclusions SCA3 is the most common subtype of SCAs in the Han population of Yunnan region.There are 15/46 incomplete penetrance nutation and 46/77 di-allele mutations.It is possible that di-allele mutations make the disease worse and accelerate clinical course progression.SCA3 and polycystic kidney disease can uncommonly happen simultaneously in a family,which perhaps suggests there are interactions between the two disease-virulence genes.

关 键 词：脊髓小脑共济失调 三核苷酸重复 突变 系谱 

分 类 号：R744.7[医药卫生—神经病学与精神病学]