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A novel m.7539C > T point mutation in the mt-tRNAAsp gene associated with multisystemic mitochondrial disease

Lookup NU author(s): Dr Diana Lehmann, Karen Baty, 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.

Publication metadata

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

Year: 2015

Volume: 25

Issue: 1

Pages: 81-84

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

Publisher: Elsevier


DOI: 10.1016/j.nmd.2014.09.008


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Funder referenceFunder name
German Ministry of Education and Research
Lily Foundation
UK NHS Highly Specialised "Rare Mitochondrial Disorders of Adults and Children" Service
096919Z/11/ZWellcome Trust Centre for Mitochondrial Research
G0601943Medical Research Council (UK) Centre for Translational Muscle Disease research