Mutation Analysis of GARS and Genotype-Phenotype Correlation in CMT2D/HMN5A in Chinese Patients

Abstract

BackgroundCMT2D is a rare subtype of axonal CMT, caused by a variant of the glycyl-tRNA synthetase (GARS) gene which is also a disease-causing gene of distal spinal muscular atrophy type V (dSMA-V) or hereditary motor neuropathy 5A (HMN5A). There were only several cases reported in China, all lacking an epidemiological study of CMT2D/ HMN5A.Methods206 patients of Chinese Han descent, clinically diagnosed with inherited peripheral neuropathy (IPN), were recruited in this study from December 20, 2012 to July 31, 2019. All patients underwent a detailed medical history screening, a neurological examination, a laboratory examination, several electrophysiological studies, and genetic testing.ResultsA total of 206 unrelated patients underwent genetic analysis. Four variants of GARS from four different families were found, including c.794C > T (p.S265F), c.374A > G (p.E125G), c.1000A > T (p.I334F), and c.781T > G (p.Y261D), with the first three being considered pathogenic. For the three pathogenic variant carriers, one was diagnosed with CMT2D, while the two others were diagnosed with HMN5A.ConclusionGARS mutation is a rare outcome of inherited peripheral neuropathy and the phenotype tends to be CMT2D or HMN5A.