title: Two pathogenic mutations in the mitochondrial DNA tRNA Leu(UUR) gene (T3258C and A3280G) resulting in variable clinical phenotypes.
abstract: We studied two patients with ragged-red fibers and combined defects of the mitochondrial respiratory chain in their muscle biopsy. One had mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, and harbored a T3258C transition in the tRNA(Leu(UUR)) gene. The other showed myopathy plus cardiomyopathy and had an A3280G mutation in the same gene. Both mutations were heteroplasmic, abundant in muscle of the patients, less abundant in blood, and still less abundant in blood from their maternal relatives. In both patients, single muscle fiber analysis revealed greater abundance of mutant genomes in ragged-red fibers than in normal fibers, supporting the pathogenicity of both mutations.
authors.affiliation: Centro de Investigación, Hospital 12 de Octubre, Avda. de Cordoba km 5.4, Madrid 28041, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Campos
authors.forename: A
authors.initials: A
authors.lastname: García
authors.forename: P
authors.initials: P
authors.lastname: del Hoyo
authors.forename: P
authors.initials: P
authors.lastname: Jara
authors.forename: M A
authors.initials: MA
authors.lastname: Martín
authors.forename: J C
authors.initials: JC
authors.lastname: Rubio
authors.forename: A
authors.initials: A
authors.lastname: Berbel
authors.forename: J R
authors.initials: JR
authors.lastname: Barberá
authors.forename: R
authors.initials: R
authors.lastname: Ribacoba
authors.forename: A
authors.initials: A
authors.lastname: Astudillo
authors.forename: A
authors.initials: A
authors.lastname: Cabello
authors.forename: J R
authors.initials: JR
authors.lastname: Ricoy
authors.forename: J
authors.initials: J
authors.lastname: Arenas
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics; D000225:Adenine; D000328:Adult; D001706:Biopsy; D009202:Cardiomyopathies / Q000235:genetics; D003596:Cytosine; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006147:Guanine; D006801:Humans; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology*; D009135:Muscular Diseases / Q000235:genetics*; D009154:Mutation; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012356:RNA, Transfer, Leu / Q000235:genetics*; D020521:Stroke / Q000235:genetics; D013941:Thymine
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine