Lookup NU author(s): Dr Kyle Thompson,
Professor Robert Taylor
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2018 John Wiley & Sons A/S. Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.
Author(s): Burke EA, Frucht SJ, Thompson K, Wolfe LA, Yokoyama T, Bertoni M, Huang Y, Sincan M, Adams DR, Taylor RW, Gahl WA, Toro C, Malicdan MCV
Publication type: Article
Publication status: Published
Journal: Clinical Genetics
Print publication date: 01/03/2018
Online publication date: 05/02/2018
Acceptance date: 05/11/2017
ISSN (print): 0009-9163
ISSN (electronic): 1399-0004
Publisher: Blackwell Publishing Ltd
PubMed id: 29120065
Altmetrics provided by Altmetric