腓骨肌萎缩症的分型与分子诊断技术

Classification and molecular diagnostic techniques of Charcot-Marie-Tooth disease

腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)是一种最常见的遗传性周围神经病,虽然常以腓骨肌萎缩和肢端骨骼畸形、运动与感觉障碍等为主要临床表现,但先天致病基因和后天影响因素的不同使该病具有高度的临床和遗传异质性;而对CMT类型的精细分类,更多是依据不同致病基因及其突变。随着近几年二代测序为代表的高通量测序技术的不断发展,已经确定了100多个CMT的致病基因和更多的新突变。本文主要阐述了CMT的遗传分型和临床特征,特别是四种常见CMT亚型的致病基因在神经细胞内参与的信号转导通路、CMT电生理和分子病理特征,以及CMT基因突变检测方法,以期为罕见病CMT的基础研究与临床诊断提供参考。

Charcot-Marie-Tooth disease(CMT)is among the most common hereditary peripheral neuropathies.Although its primary clinical manifestations are peroneal muscle atrophy,limb skeletal deformities,and distal motor and sensory disorders,it exhibits a high degree of clinical and genetic heterogeneity due to variations in congenital athogenic genes and acquired influencing factors.The precise classification of CMT types largely hinges upon different pathogenic genes and their mutations.With the continuous development of high-throughput sequencing technology,particularly next-generation sequencing,more than 100 pathogenic genes for CMT and numerous new mutations have been identified.This review mainly elaborates on the genetic classification and clinical characteristics of CMT,especially the molecular pathways of pathogenic genes in neurocytes,the electrophysiological and molecular pathological features of four common CMT subtypes,as well as methods for detecting gene mutations in CMT,aiming to provide a reference for the basic research and clinical diagnosis of this rare disease.