Lookup NU author(s): Dr Diana Lehmann,
Professor Robert Taylor
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Mitochondrial transfer RNA (mt-tRNA) mutations are the commonest sub-type of mitochondrial (mtDNA) mutations associated with human disease. We report a patient with multisytemic disease characterised by myopathy, spinal ataxia, sensorineural hearing loss, cataract and cognitive impairment in whom a novel m.7539C>T mt-tRNA(Asp) transition was identified. Muscle biopsy revealed extensive histopathological findings including cytochrome c oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for the mutation whilst single muscle fibre segregation studies revealed statistically significant higher mutation loads in COX-deficient fibres than in COX-positive fibres. Absence from control databases, hierarchical mt-tRNA mutation segregation within tissues, and occurrence at conserved sequence positions, further confirm this novel mt-tRNA mutation to be pathogenic. To date only three mt-tRNA(Asp) gene mutations have been described with clear evidence of pathogenicity. The novel m.7539C>T mt-tRNA(Asp) gene mutation extends the spectrum of pathogenic mutations in this gene, further supporting the notion that mt-tRNA(Asp) gene mutations are associated with multisystemic disease presentations. (C) 2014 The Authors. Published by Elsevier B.V.
Author(s): Lehmann D, Schubert K, Joshi PR, Baty K, Blakely EL, Zierz S, Taylor RW, Deschauer M
Publication type: Article
Publication status: Published
Journal: Neuromuscular Disorders
Print publication date: 01/01/2015
Online publication date: 28/09/2014
Acceptance date: 17/09/2014
Date deposited: 03/07/2015
ISSN (print): 0960-8966
ISSN (electronic): 1873-2364
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