Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?

C T Moraes; F Ciacci; E Bonilla; C Jansen; M Hirano; N Rao; R E Lovelace; L P Rowland; E A Schon; S DiMauro

doi:10.1172/JCI116913

Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

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Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

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Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

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Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

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Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

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Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

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Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

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Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.

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Published in Volume 92, Issue 6 on December 1, 1993
J Clin Invest. 1993;92(6):2906–2915. https://doi.org/10.1172/JCI116913.
© 1993 The American Society for Clinical Investigation

Published December 1, 1993 - Version history

We identified two patients with pathogenic single nucleotide changes in two different mitochondrial tRNA genes: the first mutation in the tRNA(Asn) gene, and the ninth known mutation in the tRNA(Leu(UUR)) gene. The mutation in tRNA(Asn) was associated with isolated ophthalmoplegia, whereas the mutation in tRNA(Leu(UUR)) caused a neurological syndrome resembling MERRF (myoclonus epilepsy and ragged-red fibers) plus optic neuropathy, retinopathy, and diabetes. Both mutations were heteroplasmic, with higher percentages of mutant mtDNA in affected tissues, and undetectable levels in maternal relatives. Analysis of single muscle fibers indicated that morphological and biochemical alterations appeared only when the proportions of mutant mtDNA exceeded 90% of the total cellular mtDNA pool. The high incidence of mutations in the tRNA(Leu(UUR)) gene suggests that this region is an "etiologic hot spot" in mitochondrial disease.

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