一个Charcot-Marie-Tooth病家系的分子遗传学分析  

Molecular genetic analysis of a Chinese family with Charcot-Marie-Tooth disease

作　　者：杨莹韵[1,2,3] 从杨[1,2,3] 孙之星[1,2,3] 田原[1,2,3] 刘辰[1,2,3] 杨威[1,2] 

机构地区：[1]中国医学科学院基础医学研究所 [2]北京协和医学院基础学院医学遗传学系,北京100005 [3]北京协和医学院

出　　处：《基础医学与临床》2010年第10期1046-1050,共5页Basic and Clinical Medicine

基　　金：美国中华医学基金会(03-785)

摘　　要：目的鉴定一个Charcot-Marie-Tooth病(CMT)家系的致病突变。方法根据家族史、临床表现和肌电图检查结果判断家系CMT分型。采集16名家系成员外周血,提取基因组DNA。针对CMT1的6个亚型,选择微卫星标记进行连锁分析。针对PMP22基因重复突变,采用实时定量PCR检测家系成员。结果本家系疾病呈常染色体显性遗传。患者均有青少年发病、缓慢进展的下肢无力症状。部分患者经查体发现下肢腱反射减弱、痛触觉减弱,下肢神经传导速度均小于30 m/s,提示为CMT1型。通过连锁分析排除了CMT1A、CMT1E以外的其他4个亚型,证实患者基因组内PMP22基因存在重复突变。结论此家系患者表型为CMT1A,其致病突变为染色体17p11.2区域内PMP22基因的重复。Objective To identify the pathogenic mutation in a large Chinese family with Charcot-Marie-Tooth disease（CMT）.Methods Medical history of the proband and a detailed family history were collected.Necessary physical examination and nerve conduction velocity/EMG testing were performed to establish the diagnosis of CMT and a primary classification.Genomic DNA was extracted from peripheral blood samples of 16 family members.Five genetic loci for six CMT1 subtypes were screened by linkage analysis using microsatellite markers.Quantitative PCR was used to detect the genomic duplication encompassing the peripheral myelin protein 22 gene（PMP22）.Results The CMT phenotype was transmitted in this family in an autosomal dominant pattern.Slow nerve conduction velocity（10～30 m/s） was observed in all of the four patients who participated in the electrophysiologic testing.By linkage analysis,all CMT1 subtypes were excluded except the CMT1A and CMT1E locus,both of them are positive for PMP22 gene on chromosome 17p11.2 region.Heterogeneous duplication of the PMP22 gene was detected in patients,but not in unaffected family members.Conclusion The disease in the family was ascertained to be CMT1A,and was caused by the PMP22 duplication.

关 键 词：CHARCOT-MARIE-TOOTH病 PMP22 重复突变 定量PCR 

分 类 号：R394[医药卫生—医学遗传学]