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Lookup NU author(s): Dr John Yarham, Dr Charlotte Alston, Emeritus Professor Doug Turnbull, Professor Bobby McFarlandORCiD, Professor Robert Taylor
Mitochondrial tRNA point mutations are important causes of human disease, and have been associated with a diverse range of clinical phenotypes. Definitively proving the pathogenicity of any given mt-tRNA mutation requires combined molecular, genetic and functional studies. Subsequent evaluation of the mutation using a pathogenicity scoring system is often very helpful in concluding whether or not the mutation is causing disease. Despite several independent reports linking the m.3291T>C mutation to disease in humans, albeit in association with several different phenotypes, its pathogenicity remains controversial. A lack of conclusive functional evidence and an over-emphasis on the poor evolutionary conservation of the affected nucleotide have contributed to this controversy. Here we describe an adult patient who presented with deafness and lipomas and evidence of mitochondrial abnormalities in his muscle biopsy, who harbours the m.3291T>C mutation, providing conclusive evidence of pathogenicity through analysis of mutation segregation with cytochrome c oxidase (COX) deficiency in single muscle fibres, underlining the importance of performing functional studies when assessing pathogenicity. (C) 2012 Elsevier B.V. All rights reserved.
Author(s): Yarham JW, Blakely EL, Alston CL, Roberts ME, Ealing J, Pal P, Turnbull DM, McFarland R, Taylor RW
Publication type: Article
Publication status: Published
Journal: Journal of the Neurological Sciences
Year: 2013
Volume: 325
Issue: 1-2
Pages: 165-169
Print publication date: 15/02/2013
Date deposited: 30/07/2013
ISSN (print): 0022-510X
ISSN (electronic): 1878-5883
Publisher: Elsevier BV
URL: http://dx.doi.org/10.1016/j.jns.2012.12.003
DOI: 10.1016/j.jns.2012.12.003
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