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Familial myopathy: New insights into the T14709C mitochondrial tRNA mutation
Author(s) -
McFarland Robert,
Schaefer Andrew M.,
Gardner Julie L.,
Lynn Stephen,
Hayes Christine M.,
Barron Martin J.,
Walker Mark,
Chinnery Patrick F.,
Taylor Robert W.,
Turnbull Douglass M.
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20004
Subject(s) - heteroplasmy , mitochondrial myopathy , transfer rna , genetics , mitochondrial dna , mutation , biology , mitochondrial disease , phenotype , myopathy , gene , rna
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 RNA Glu (mt‐tRNA Glu ) gene. Extraordinarily, this mutation has attained homoplasmy (100% mutated mt‐tRNA Glu ) 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. Ann Neurol 2004;55:000–000