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Lookup NU author(s): Professor Bobby McFarlandORCiD,
Dr Andrew Schaefer,
Dr Julie Murphy,
Dr Stephen Lynn,
Dr Martin Barron,
Professor Mark Walker,
Professor Patrick Chinnery,
Professor Robert Taylor,
Emeritus Professor Doug Turnbull
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We have defined the genetic defect in a large family first described in one of the earliest reports of suspected mitochondrial myopathy, as the mutation T14709C in the mitochondrial transfer RNAGlu (mt-tRNA Glu) gene. Extraordinarily, this mutation has attained homoplasmy (100% mutated mt-tRNAGlu) on at least three independent occasions in this family and has done so in one individual who remains asymptomatic with no clinical evidence of disease. Heteroplasmy (dual populations of mutated and wild-type mtDNA) usually is regarded as one of the primary diagnostic criteria for pathogenicity and previous reports of the T14709C mutation detail heteroplasmy in a variety of tissues. In contrast, homoplasmy of mt-tRNA mutations generally has been regarded as evidence of a benign nature, with rare exceptions that result in organ-specific phenotypes. Discovering that T14709C, a common and severe mt-tRNA mutation, can attain homoplasmy without symptoms or clinical signs of disease has profound implications for the identification and prevalence of other pathogenic mt-tRNA mutations. Furthermore, variation in phenotype between homoplasmic individuals implies a crucial contribution from the nuclear genetic environment in determining the clinical outcome of mt-tRNA mutations.
Author(s): McFarland R, Schaefer AM, Gardner JL, Lynn S, Hayes CM, Barron MJ, Walker M, Chinnery PF, Taylor RW, Turnbull DM
Publication type: Article
Publication status: Published
Journal: Annals of Neurology
Print publication date: 18/02/2004
ISSN (print): 0364-5134
ISSN (electronic): 1531-8249
Publisher: John Wiley & Sons, Inc.
PubMed id: 15048886
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