Abstract: Objective To analyse the location of pathogenic genes of autosomal dominant Charcot-Marie-Tooth disease (CMT, peroneal atrophy) in a Chinese pedigree. Methods The pedigree of autosomal dominant Charcot-Marie-Tooth disease was confirmed by genetic pattern, clinical manifestation and neuromuscular electrophysiological and laboratory examinations. Linkage analysis was performed by using 37 microsatellite genetic markers for the autosomal dominant Charcot-Marie-Tooth disease pedigree. Thirty-seven microsatellite genetic markers covering 16 genetic loci were linked to 20 kinds of known autosomal dominant Charcot -Marie-Tooth disease. The 16 genetic loci were 17p11.2-p12 (D17S839, D17S122, D17S793), 1q22 (D1S426, D1S2771), 16p12.3-p13.1 (D16S764, D16S3137), 10q21.1 (D10S546, D10S561, D10S581), 1p36.2 (D1S2845, D1S2893, D1S2660), 3q21 (D3S1273, D3S1292), 12q23 (D12S1329, D12S105), 7p15 (D7S2562, D7S516), 8p21 (D8S552, D8S265), 7q11-q21 (D7S634, D7S669), 12q12-q13 (D12S1663, D12S368, D12S1632), 8q13-q21 (D8S286, D8S548), 12q24.3 (D12S1679, D12S86), 10q24 (D10S554, D10S571, D10S1863), 19p12-p13 (D19S916, D19S433) and 1p34-p35 (D1S489, D1S432). Results All microsatellite genetic markers were amplified successfully, and polymorphisms were presented on every genetic loci. The examined pedigree of Charcot-Marie-disease was autosomal dominant inheritance. Three patients did not present the same allele on the 16 genetic loci. Linkage analysis indicated that the pathogenic genes in all the members of this pedigree did not link with the 16 known pathogenic genetic loci in autosomal dominant Charcot-Marie-Tooth disease. Conclusion The diagnosis of autosomal dominant Charcot-Marie-Tooth disease in this pedigree is confirmed, but do not coincide with the diagnostic criteria of the known types of this disease recommended by European Neuromuscular Center (ENMC). It is suggested that autosomal dominant Charcot?Marie?Tooth disease in this Chinese pedigree may be a new type caused by other pathogenic genes.

Key words: Genetic diseases, inborn, Genes, dominant, Charcot-Marie-Tooth disease, Pedigree, Polymerase chain reaction

摘要： 目的   定位分析一常染色体显性遗传腓骨肌萎缩症家系的致病基因。方法   依据家系图、临床表现、神经肌肉电生理学及实验室检查结果，明确诊断一常染色体显性遗传腓骨肌萎缩症家系。采用16 个基因位点的37 个短串联重复序列（STR）标记方法进行连锁分析，以覆盖目前已经发现的20 种常染色体显性遗传腓骨肌萎缩症亚型的16 个致病基因位点。结果   所选择的37 个STR 标记均发生扩增反应，每一基因位点均呈现多态性。受检腓骨肌萎缩症家系呈常染色体显性遗传，其中3 例患者在17p11.2-p12、1q22、16p12.3-p13.1、10q21.1、1p36.2、3q21、12q23、7p15、8p21、7q11-q21、12q12-q13、8q13-q21、12q24.3、10q24、19p12-p13 及1p34-p35 共16 个基因位点的单倍体型均不存在等位基因共享，且家系所有成员致病基因均与16 个已知常染色体显性遗传腓骨肌萎缩症致病基因位点不连锁。结论   研究过程中每一基因位点所用STR 标记为2 ~ 3 个，基本可以排除染色体互换，常染色体显性遗传腓骨肌萎缩症家系诊断依据充分；根据欧洲神经肌肉病中心制订的确诊标准，可排除为已知类型的常染色体显性遗传腓骨肌萎缩症家系。推测为一新型腓骨肌萎缩症致病基因所引起的常染色体显性遗传腓骨肌萎缩症家系。

关键词: 遗传性疾病, 先天性, 基因, 显性, 夏科-马里-图斯病, 系谱, 聚合酶链反应