title: Maternally inherited cardiomyopathy and hearing loss associated with a novel mutation in the mitochondrial tRNA(Lys) gene (G8363A).
abstract: A novel G8363A mutation in the mtDNA tRNA(Lys) gene was associated, in two unrelated families, with a syndrome consisting of encephalomyopathy, sensorineural hearing loss, and hypertrophic cardiomyopathy. Muscle biopsies from the probands showed mitochondrial proliferation and partial defects of complexes I, III, and IV of the electron-transport chain. The G8363A mutation was very abundant (>95%) in muscle samples from the probands and was less copious in blood from 18 maternal relatives (mean 81.3% +/- 8.5%). Single-muscle-fiber analysis showed significantly higher levels of mutant genomes in cytochrome (c) oxidase-negative fibers than in cytochrome (c) oxidase-positive fibers. The mutation was not found in >200 individuals, including normal controls and patients with other mitochondrial encephalomyopathies, thus fulfilling accepted criteria for pathogenicity.
authors.affiliation: H. Houston Merritt Center for Muscular Research and Related Disorders, Department of Neurology, Columbia University 10032, New York, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: S C
authors.initials: SC
authors.lastname: Mak
authors.forename: M
authors.initials: M
authors.lastname: El-Schahawi
authors.forename: C
authors.initials: C
authors.lastname: Casali
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: T Z
authors.initials: TZ
authors.lastname: Baram
authors.forename: R E
authors.initials: RE
authors.lastname: Madrid
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006311:Hearing Disorders / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012357:RNA, Transfer, Lys / Q000235:genetics*; D013577:Syndrome
chemical_list: D000077278:RNA, Mitochondrial; D012357:RNA, Transfer, Lys; D012313:RNA