Journal article
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy
MS Van Der Knaap, M Bugiani, MI Mendes, LG Riley, DEC Smith, J Rudinger-Thirion, M Frugier, M Breur, J Crawford, J Van Gaalen, M Schouten, M Willems, Q Waisfisz, FT Mau-Them, RJ Rodenburg, RJ Taft, B Keren, J Christodoulou, C Depienne, C Simons Show all
Neurology | LIPPINCOTT WILLIAMS & WILKINS | Published : 2019
Abstract
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.MethodsWe 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.ResultsPatients had a combination of early-onset deafness and later-ons..
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Awarded by National Institute of Mental Health
Funding Acknowledgements
This study was in part financed by the Australian National Health and Medical Research Council (NHMRC 1068278), the Victorian Government's Operational Infrastructure Support Program, and the ZonMw grant 40-00812-98-11005. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the NIH, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS.