Mutation spectrum of Charcot‐Marie‐Tooth disease among the Han Chinese in Taiwan

• Published in: Annals of clinical and translational neurology Vol. 6; no. 6; pp. 1090 - 1101
• Main Authors: Hsu, Yun‐Hsin, Lin, Kon‐Ping, Guo, Yuh‐Cherng, Tsai, Yu‐Shuen, Liao, Yi‐Chu, Lee, Yi‐Chung
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2019; John Wiley and Sons Inc; Wiley
• Subjects: Adolescent; Adult; Asians; Bioinformatics; Charcot-Marie-Tooth Disease - genetics; Child; Child, Preschool; DNA Mutational Analysis; Genetic counseling; Genomes; Genotype & phenotype; Humans; Middle Aged; Mutation; Patients; Software; Taiwan; Young Adult; Taiwan
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.50797

Objective Charcot‐Marie‐Tooth disease (CMT) is a clinically and genetically heterogeneous group of inherited neuropathies. Mutations in more than 90 genes have been implicated in CMT; however, the mutational spectrum of CMT in Chinese population remains obscure. This study aims to provide a comprehensive overview of the frequency of mutations in Taiwanese patients with CMT and look for genotype‐phenotype correlations. Methods Mutational analyses were performed on 427 unrelated Taiwanese patients with CMT by polymorphic microsatellite markers analysis or real‐time fluorescent PCR for PMP22 duplication, Sanger sequencing for GJB1 mutations, and targeted sequencing covering 124 genes causing or relevant to inherited neuropathies. We also correlated the genotypes with the phenotypic features, such as age at disease onset and ulnar motor nerve conduction velocity. Results Pathogenic mutations were identified in 312 patients (73.1%; 312/427), including 208 patients with a PMP22 duplication, 40 patients with a GJB1 mutation, and 64 patients with a mutation in one of other 18 CMT genes. A confirmed molecular diagnosis was achieved in 84.4% (266/315) of the patients with demyelinating CMT and 41.1% (46/112) of the patients with axonal CMT. Mutations in MPZ, MFN2, or NEFL are the most frequent disease causes in patients with infantile‐onset CMT (≤2 years), while PMP22 duplications and mutations in GJB1, MFN2, or MPZ are the frequent causes among patients with childhood‐ or adolescence‐onset CMT (3–9 years). Interpretation This study provides a genotype‐phenotype landscape of CMT in Taiwan and highlights the unique spectrum of CMT genes frequencies among patients of Chinese origin.