Pathogenic genes of autosomal dominant Charcot⁃Marie⁃Tooth disease in a Chinese pedigree

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 ⁃ Tooth 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.

DOI：10.3969/j.issn.1672-6731.2010.03.018