The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 among the han Chinese in Taiwan
Journal
PLoS ONE
Journal Volume
6
Journal Issue
12
Date Issued
2011
Author(s)
Chih-Chao Yang
Abstract
Background: Charcot-Marie-Tooth disease type 2 (CMT2) is a clinically and genetically heterogeneous group of inherited axonal neuropathies. The aim of this study was to extensively investigate the mutational spectrum of CMT2 in a cohort of patients of Han Chinese. Methodology and Principal Findings: Genomic DNA from 36 unrelated Taiwanese CMT2 patients of Han Chinese descent was screened for mutations in the coding regions of the MFN2, RAB7, TRPV4, GARS, NEFL, HSPB1, MPZ, GDAP1, HSPB8, DNM2, AARS and YARS genes. Ten disparate mutations were identified in 14 patients (38.9% of the cohort), including p.N71Y in AARS (2.8%), p.T164A in HSPB1 (2.8%), and p.[H256R]+[R282H] in GDAP1 (2.8%) in one patient each, three NEFL mutations in six patients (16.7%) and four MFN2 mutations in five patients (13.9%). The following six mutations were novel: the individual AARS, HSPB1 and GDAP1 mutations and c.475-1G>T, p.L233V and p.E744M mutations in MFN2. An in vitro splicing assay revealed that the MFN2 c.475-1G>T mutation causes a 4 amino acid deletion (p.T159_Q162del). Despite an extensive survey, the genetic causes of CMT2 remained elusive in the remaining 22 CMT2 patients (61.1%). Conclusions and Significance: This study illustrates the spectrum of CMT2 mutations in a Taiwanese CMT2 cohort and expands the number of CMT2-associated mutations. The relevance of the AARS and HSPB1 mutations in the pathogenesis of CMT2 is further highlighted. Moreover, the frequency of the NEFL mutations in this study cohort was unexpectedly high. Genetic testing for NEFL and MFN2 mutations should, therefore, be the first step in the molecular diagnosis of CMT2 in ethnic Chinese. ? 2011 Lin et al.
SDGs
Other Subjects
genomic DNA; AARS gene; adolescent; adult; article; Asian; Charcot Marie Tooth Disease type 2; child; clinical article; cohort analysis; controlled study; DNA determination; DNM2 gene; female; GARS gene; GDAP1 gene; gene; gene deletion; gene mutation; genetic analysis; genetic association; Han Chinese; hereditary motor sensory neuropathy; HSPB1 gene; HSPB8 gene; human; in vitro study; male; MFN2 gene; molecular pathology; mpz gene; mutation rate; mutational analysis; NEFL gene; preschool child; RAB7 gene; RNA splicing; Taiwan; Taiwanese; TRPV4 gene; YARS gene; amino acid sequence; animal; Asian; cattle; ethnic group; ethnology; genetics; hereditary motor sensory neuropathy; middle aged; molecular genetics; mouse; mutation; nucleotide sequence; rat; Adolescent; Adult; Amino Acid Sequence; Animals; Asian Continental Ancestry Group; Base Sequence; Cattle; Charcot-Marie-Tooth Disease; Child; Child, Preschool; Cohort Studies; DNA Mutational Analysis; Ethnic Groups; Female; Humans; Male; Mice; Middle Aged; Molecular Sequence Data; Mutation; Rats; Taiwan; Young Adult
Type
journal article