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Clinical features of the pathogenic m.5540G > A mitochondrial transfer RNA tryptophan gene mutation

Lookup NU author(s): Dr Yi Ng, Steven Hardy, Professor Robert Taylor



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Mitochondrial DNA disease is one of the most common groups of inherited neuromuscular disorders and frequently associated with marked phenotypic and genotypic heterogeneity. We describe an adult patient who initially presented with childhood-onset ataxia without a family history and an unremarkable diagnostic muscle biopsy. Subsequent multi-system manifestations included basal ganglia calcification, proteinuria, cataract and retinitis pigmentosa, prompting a repeat muscle biopsy that showed features consistent with mitochondrial myopathy 13 years later. She had a stroke with restricted diffusion change in the basal ganglia and internal capsule at age 44 years. Molecular genetic testing identified a previously-reported pathogenic, heteroplasmic mutation in the mitochondrial-encoded transfer RNA tryptophan (MT-TW) gene which based on family studies was likely to have arisen de novo in our patient. Interestingly, we documented an increase in the mutant mtDNA heteroplasmy level in her second biopsy (72% compared to 56%), reflecting the progression of clinical disease. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (

Publication metadata

Author(s): Ng YS, Hardy SA, Shrier V, Quaghebeur G, Mole DR, Daniels MJ, Downes SM, Freebody J, Fratter C, Hofer M, Nemeth AH, Poulton J, Taylor RW

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2016

Volume: 26

Issue: 10

Pages: 702-705

Print publication date: 01/10/2016

Online publication date: 17/08/2016

Acceptance date: 15/08/2016

Date deposited: 21/12/2016

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Pergamon Press


DOI: 10.1016/j.nmd.2016.08.009


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Funder referenceFunder name
MR/J010448/1Medical Research Council
096919/Z/11/ZWellcome Trust