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Familial Myopathy: New Insights into the T14709C Mitochondrial tRNA Mutation

Lookup NU author(s): Professor Bobby McFarlandORCiD, Dr Andrew Schaefer, Dr Julie Murphy, Dr Stephen Lynn, Christine Hayes, 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.

Publication metadata

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

Year: 2004

Volume: 55

Issue: 4

Pages: 478-484

Print publication date: 18/02/2004

ISSN (print): 0364-5134

ISSN (electronic): 1531-8249

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/ana.20004

PubMed id: 15048886


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