Mutation Analysis of Gap Junction Protein Beta 1 and Genotype-Phenotype Correlation in X-linked Charcot-Marie- Tooth Disease in Chinese Patients

• Published in: Chinese medical journal Vol. 129; no. 9; pp. 1011 - 1016
• Main Authors: Sun, Bo, Chen, Zhao-Hui, Ling, Li, Li, Yi-Fan, Liu, Li-Zhi, Yang, Fei, Huang, Xu-Sheng
• Format: Journal Article
• Language: English
• Published: China Wolters Kluwer - Medknow Publications 05-05-2016; Medknow Publications and Media Pvt. Ltd; Lippincott Williams & Wilkins Ovid Technologies; Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer
• Subjects: Adolescent; Adult; Analysis; Bioinformatics; Charcot-Marie-Tooth disease; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - physiopathology; Computational Biology; Connexin 32; Electrophysiology; Gap Junction Protein Beta 1; Genetic Mutation; X-linked Charcot–Marie–Tooth Disease; Connexins - genetics; Deoxyribonucleic acid; DNA; Female; Gap Junction beta-1 Protein; Gene expression; Gene mutation; Genetic aspects; Genetic testing; Genomes; Genomics; Genotype; Humans; Laboratories; Male; Middle Aged; Mutation; Mutation, Missense; Nervous system; Neural Conduction; Neurology; Original; Phenotype; Protein research; Proteins; Studies; 中国人民解放军; 基因型; 基因突变; 患者; 突变分析; 表型; 连锁; 间隙连接蛋白; Gap Junction Protein Beta 1; Electrophysiology; X-linked Charcot-Marie-Tooth Disease; Connexin 32; Genetic Mutation
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.180511

Background： Among patients with Charcot-Marie-Tooth disease （CMT）, the X-linked variant （CMTX） caused by gap junction protein beta 1 （GJB1） gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 （CX32）. CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered. Methods： We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People＇s Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX 1. Results： Nine GJBI mutations （c.283G〉A, c.77C〉T, c.643C〉T, c.515C〉T, c.191G〉A, c.610C〉T, c.490C〉T, c.491G〉A, and c.44G〉A） were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were 〈 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C〉T, c.191G〉A, and c.610C〉T, were revealed and bioinformatics analyses indicated high pathogenicity. Conclusions： The three novel missense mutations within the GJB1 gene broaden the mutational diversity ofCMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.