A Novel Mutation of GARS in a Chinese Family With Distal Hereditary Motor Neuropathy Type V

作者：Yu, Xueying; Chen, Bin; Tang, Hefei; Li, Wei; Fug, Ying; Zhang, Zaiqiang^*; Yan, Yaping^*

来源：Frontiers in Neurology, 2018, 9: 571.

DOI：10.3389/fneur.2018.00571

• dHMN-V
• CMT2D
• Novel mutation
• GARS gene
• silico analysis

Glycyl-tRNA synthetase (GARS) gene mutations have been reported to be associated with Charcot-Marie-Tooth disease 2D and distal hereditary motor neuropathy type V (dHMN-V). In this study, we report a novel GARS mutation in a Chinese family with dHMN-V. Clinical, electromyogram, genetic, and functional data were explored. The proband was an 11-year-old girl presented with progressive distal limb muscle weakness and atrophy due to peripheral motor neuropathy for 1 year. Another five members from three successive generations of the family showed similar symptoms during their first to second decades and demonstrated an autosomal dominant inheritance. The results of genetic testing revealed a novel c.383T>G mutation in the GARS gene in the affected individuals, showing apparent genetic cosegregation. Further bioinformatic analyses showed that the c.383T > G mutation resulted in L128R alteration in the second functional protein domain, and the mutation site was well conserved among different species. In silico analysis predicted that this mutation probably affected protein function. In vitro, this GARS mutation led to a different protein localization pattern than that of the wild-type enzyme. The study found a novel GARS mutation of c.383T > G causing dHMN-V with subcellular localization abnormity in a genetic cosegregation family. These findings broaden the mutational spectrum of GARS.

• 出版日期2018-7-23
• 单位首都医科大学; 陕西师范大学