Mutations in the mitochondrial tryptophanyl-tRNA synthetase cause growth retardation and progressive leukoencephalopathy.

ABSTRACT:

Background

Mutations in mitochondrial aminoacyl tRNA synthetases form a subgroup of mitochondrial disorders often only perturbing brain function by affecting mitochondrial translation. Here we report two siblings with mitochondrial disease, due to compound heterozygous mutations in the mitochondrial tryptophanyl-tRNA synthetase (WARS2) gene, presenting with severe neurological symptoms but normal mitochondrial function in skeletal muscle biopsies and cultured skin fibroblasts.

Methods

Whole exome sequencing on genomic DNA samples from both subjects and their parents identified two compound heterozygous variants c.833T>G (p.Val278Gly) and c.938A>T (p.Lys313Met) in the WARS2 gene as potential disease-causing variants. We generated patient-derived neuroepithelial stem cells and

SUBMITTER: Maffezzini C 

PROVIDER: S-EPMC6565557 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature