[A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement].

Abstract

BACKGROUND:

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy; symptoms include distal wasting and weakness, usually with some sensory impairment. The clinical course is typically benign and the disease is not life threatening; however, in some cases, severe phenotypes include serious respiratory distress.

CASE REPORT:

Here we describe a 45-year-old woman with a long course of motor-dominant neuropathy. Distal weakness appeared in childhood and became worse with age. After a diagnosis of CMT type 2, the symptoms progressed, and in her fourth decade, facial and respiratory muscle weakness appeared, ultimately requiring non-invasive mechanical ventilation. There was no family history of CMT. Comprehensive analysis of known CMT-related genes revealed a novel heterozygous c.815T>A, p.L218Q mutation in glycyl-tRNA synthetase (GARS), a causative gene for both CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). This mutation was considered pathogenic based on molecular evidence; notably, it was unique in that all other reported GARS mutations associated with severe phenotypes are located in an anticodon-binding domain, while in this case in an apparently non-functional region of the GARS gene. Not a simple loss-of-function mechanism, but rather gain-of-function mechanisms have also been reported in GARS mutations. This case provided useful information for understanding the mechanism of CMT2D/dSMA-V.

• Authors: Nobuko Kawakami, Kenichi Komatsu, Hirofumi Yamashita, Kengo Uemura, Nobuyuki Oka, Hiroshi Takashima, Ryosuke Takahashi
• Journal: Rinsho shinkeigaku = Clinical neurology (Rinsho Shinkeigaku) Vol. 54 Issue 11 Pg. 911-5 ( 2014) ISSN: 1882-0654 [Electronic] Japan
• PMID: 25420567 (Publication Type: Case Reports, English Abstract, Journal Article)

Chemical References

• Glycine-tRNA Ligase

Topics

• Charcot-Marie-Tooth Disease (genetics, physiopathology)
• Facial Muscles (physiopathology)
• Female
• Glycine-tRNA Ligase (genetics)
• Humans
• Middle Aged
• Mutation
• Respiratory Muscles (physiopathology)