Clinical and Genetic Features in a Series of Eight Unrelated Patients with Neuropathy Due to Glycyl-tRNA Synthetase (GARS) Variants

Natalie Forrester, Rohini Rattihalli, Rita Horvath, Lorenzo Maggi, Adnan Manzur, Geraint Fuller, Nicholas Gutowski, Julia Rankin, David Dick, Christopher Buxton, Mark Greenslade, Anirban Majumdar

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Pathogenic variants in the Glycyl-tRNA synthetase gene cause the allelic disorders Charcot-Marie-Tooth disease type 2D and distal hereditary motor neuropathy type V. We describe clinical features in 8 unrelated patients found to have Glycyl-tRNA synthetase variants by Next Generation Sequencing. In addition to upper limb predominant symptoms, other presentations included failure to thrive, feeding difficulties and lower limb dominant symptoms. Variability in the age at testing ranged from 14 months to 59 years. The youngest being symptomatic from 3 months and ventilator-dependent. Sequence variants were reported as pathogenic, p.(Glu125Lys), p.(His472Arg); likely pathogenic, p.(His216Arg), p.(Gly327Arg), p.(Lys510Gln), p.(Met555Val); and of uncertain significance, p.(Arg27Pro). Our case series describes novel Glycyl-tRNA synthetase variants and demonstrates the clinical utility of Next Generation Sequencing testing for patients with hereditary neuropathy. Identification of novel variants by Next Generation Sequencing illustrates that there exists a wide spectrum of clinical features and supports the newer simplified classification of neuropathies.

Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalJournal of neuromuscular diseases
Volume7
Issue number2
DOIs
Publication statusPublished - 20 Mar 2020

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