Department of Clinical Genetics, Institute of Genetics and Hospital for Genetic Disease, Osmania University, Hyderabad, Telangana, India.
Neurol India. 2024 Sep 1;72(5):1081-1083. doi: 10.4103/neurol-india.NI_837_19. Epub 2024 Oct 19.
Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disorder. As more genes are identified and overlapping of neuropathy phenotypes, the traditional classification of CMT often proves inadequate. A young male with typical clinical features was suspected to have CMT, but family history about the inheritance pattern and distinct features suggestive of particular subtypes were lacking. He was directly evaluated by whole exome sequencing (WES). The libraries from extracted DNA were sequenced on Illumina sequencing platform. The variant detected in WES was confirmed by Sanger sequencing. WES shows a likely pathogenic hemizygous missense variation in exon 2 of the gap junction protein beta 1(GJB1) gene (chrX: 70444104; C > T; Depth: 66x) that results in the substitution of cysteine for arginine at codon 183 (p.Arg183Cys). This novel variation expands the spectrum of GJB1 mutations associated with X-linked CMT (CMTX) to establish a specific genetic cause.
腓骨肌萎缩症（CMT）是一种遗传异质性疾病。随着越来越多的基因被发现，神经病变表型出现重叠，传统的 CMT 分类往往证明是不够的。一名具有典型临床特征的年轻男性被怀疑患有 CMT，但缺乏关于遗传模式和特定亚型的明显特征的家族史。他直接通过外显子组测序（WES）进行评估。从提取的 DNA 中制备文库，并在 Illumina 测序平台上进行测序。在 WES 中检测到的变异通过 Sanger 测序进行确认。WES 显示在间隙连接蛋白β 1（GJB1）基因的外显子 2 中存在一个可能的致病性杂合错义变异（chrX：70444104；C > T；深度：66x），导致密码子 183 的精氨酸被半胱氨酸取代（p.Arg183Cys）。这种新的变异扩展了与 X 连锁腓骨肌萎缩症（CMTX）相关的 GJB1 突变谱，从而确定了特定的遗传病因。
