Familial mitochondrial encephalomyopathy (MERRF): Genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease

Douglas C. Wallace, Xianxian Zheng, Marie T. Lott, John M. Shoffner, Judith A. Hodge, Richard I. Kelley, Charles M. Epstein, Linton C. Hopkins

Research output: Contribution to journalArticlepeer-review

Abstract

A large MERRF pedigree permitted the direct testing of the predictions for a mitochondrial DNA (mtDNA) mutation. A mtDNA mutation was demonstrated by proving maternal inheritance and by identifying specific deficiencies in muscle energetics and mitochondrial respiratory complexes I and IV. mtDNA heteroplasmy (a mixture of mutant and wild-type mtDNAs) was demonstrated by showing variation in the mitochondrial energetic capacity between family members. The phenotypic consequences of differential tissue-specific reliance on mitochondrial ATP was shown by correlating individual respiratory deficiency with the nature and severity of patients' clinical manifestations. The observed spectrum of clinical manifestations resulting from this heteroplasmic mtDNA mutation implies that mtDNA disease may be much more prevalent than previously anticipated.

Original languageEnglish (US)
Pages (from-to)601-610
Number of pages10
JournalCell
Volume55
Issue number4
DOIs
StatePublished - Nov 18 1988

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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