MATERNALLY INHERITED CARDIOMYOPATHY AND HEARING-LOSS ASSOCIATED WITH A NOVEL MUTATION IN THE MITOCHONDRIAL TRNA(LYS) GENE (G8363A)

A novel G8363A mutation in the mtDNA tRNA(Lys) gene was associated, in two unrelated families, with a syndrome consisting of encephalomyopat hy, sensorineural hearing loss, and hypertrophic cardiomyopathy. Muscl e biopsies from the probands showed mitochondrial proliferation and pa rtial defects of complexes I, III, and IV of the electron-transport ch ain. The G8363A mutation was very abundant (> 95%) in muscle samples f rom the probands and was less copious in blood from 18 maternal relati ves (mean 81.3% +/- 8.5%). Single-muscle-fiber analysis showed signifi cantly higher levels of mutant genomes in cytochrome c oxidase-negativ e fibers than in cytochrome c oxidase-positive fibers. The mutation wa s not found in > 200 individuals, including normal controls and patien ts with other mitochondrial encephalomyopathies, thus fulfilling accep ted criteria for pathogenicity.