Journal Article

Clinical and Genetic Features of Chinese X-linked Charcot-Marie-Tooth Type 1 Disease

Yuan-Yuan Lu He Lyu Su-Qin Jin Yue-Huan Zuo Jing Liu Zhao-Xia Wang Wei Zhang Yun Yuan

2017

Overview

Background： X-linked Charcot-Marie-Tooth type 1 （CMT1 X） disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein （GJB1） gene （also known as connexin 32）. This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations. Methods： A total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJBI mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing （NGS）. Nucleotide alternations were confirnled with Sanger sequencing. Results： The CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years （ranging from 1 year to 42 years）. The sudden onset of cerebral symptoms appeared in four patients （ 18.2%）： two were initial symptoms. One case had constant central nervous system （CNS） signs. There were 19 different heterozygous mutations, including 15 known mutations and tbur novel mutations （c. II5G〉T, c.380T〉A, c.263C〉A, and c.818_819insGGGCT）. Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 （TM1）, 4.5% in TM2, 27.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 （EC1）, 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-ternlinal domain. CMTIX with CNS impairment appeared in five （22.7%） of these patients. Conclusions： This study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJBI gene were hotspot in Chinese CMT1X patients.

• Publisher: Medknow Publications and Media Pvt. Ltd,Lippincott Williams & Wilkins Ovid Technologies,Department of Neurology, Peking University First Hospital, Beijing 100034, China,Medknow Publications & Media Pvt Ltd,Wolters Kluwer
• Subject: Adolescent / Adult / Central Nervous System - metabolism / Charcot-Marie-Tooth disease / Charcot-Marie-Tooth Disease - genetics / Charcot-Marie-Tooth Disease - pathology / Child / Child, Preschool / Connexin 32; Gap Junction Beta-1 Protein; Neuropathy; X-linked Charcot-Marie-Tooth Type 1 / Connexins - genetics / DNA Mutational Analysis / Electrophysiology / Families & family life / Female / Gap Junction beta-1 Protein / Gene mutations / Genes / Genetic aspects / Genotype / Humans / Infant / Male / Mutation / Nervous system / Neurology / Original / Patients / Phenotype / Proteins / Retrospective Studies / Risk factors / Young Adult / 中国 / 中枢神经系统 / 临床资料 / 北京大学第一医院 / 基因突变 / 连锁 / 遗传特点 / 间隙连接蛋白