title: Clinical and genetic spectra of Charcot-Marie-Tooth disease in Chinese Han patients.
abstract: Charcot-Marie-Tooth disease (CMT) is a common hereditary motor and sensory neuropathy. Epidemiological data for Chinese CMT patients are few. This study aimed to analyze the electrophysiological and genetic characteristics of Chinese Han patients. A total of 106 unrelated patients with the clinical diagnosis of CMT were included. Clinical examination, nerve conduction studies (NCS), next-generation sequencing (NGS), and bioinformatic analyses were performed. Genetic testing was performed for 82 patients; 27 (33%) patients carried known CMT-associated gene mutations. PMP22 duplication was detected in 10 (12%) patients and GJB1 mutations in 9 (11%) patients. The mutation rate was higher in patients with a positive family history than in the sporadic cases (50% vs. 27%, p < 0.05). Six novel CMT-associated gene mutations including BSCL2 (c.461C>T), LITAF (c.32C>G), MFN2 (c.497C>T), GARS (c.794C>T), NEFL (c.280C>T), and MPZ (c.440T>C) were discovered. All except the LITAF (c.32C>G) mutation were identified as "disease causing" via bioinformatic analyses. In this Chinese Han population, the frequency of PMP22 gene duplication in those with CMT1 was slightly (50% vs. 70%-80%) less than in Western/Caucasian populations. The novel CMT-associated gene mutations broaden the mutation diversity of CMT1. NGS should be considered for genetic analyses in CMT patients.
authors.affiliation: Department of Neurology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ling
authors.affiliation: Department of Neurology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Neurology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000208:ethnology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology*; D019295:Computational Biology; D017630:Connexins / Q000235:genetics*; D004576:Electromyography; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics / Q000502:physiology; D012189:Retrospective Studies; D055815:Young Adult; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D009185:Myelin Proteins; D000097002:Gap Junction beta-1 Protein; C073687:PMP22 protein, human
keywords: Charcot-Marie-Tooth disease; electrophysiology; gene mutation; next-generation sequencing