Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy.

ABSTRACT:

Objective

To describe the leukodystrophy caused by pathogenic variants in LARS2 and KARS, encoding mitochondrial leucyl transfer RNA (tRNA) synthase and mitochondrial and cytoplasmic lysyl tRNA synthase, respectively.

Methods

We composed a group of 5 patients with leukodystrophy, in whom whole-genome or whole-exome sequencing revealed pathogenic variants in LARS2 or KARS. Clinical information, brain MRIs, and postmortem brain autopsy data were collected. We assessed aminoacylation activities of purified mutant recombinant mitochondrial leucyl tRNA synthase and performed aminoacylation assays on patients' lymphoblasts and fibroblasts.

Results

Patients had a combination of early-onset deafness and later-onset neurologic deterioration caused b

SUBMITTER: van der Knaap MS 

PROVIDER: S-EPMC9281382 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature