title: Clinical and cellular consequences of the mutation m.12300G>A in the mitochondrial tRNA(Leu(CUN)) gene.
abstract: We report, for the first time, a patient with an overlap MERRF-NARP syndrome who carries the mutation m.12300G>A in the mitochondrial tRNA(Leu(CUN)) gene. The mutation was heteroplamic and more abundant in her muscle and fibroblast than in blood from her oligosymptomatic mother. Single muscle fiber analysis revealed that the proportion of mutant mtDNA in ragged red fibers was higher than that in normal fibers. Combined defects of mitochondrial respiratory chain complexes were detected in muscle, fibroblasts and transmitochondrial hybrid cells. Significant reduction of total ATP and mitochondrial membrane potential and an increased production of reactive oxygen species were observed.
authors.affiliation: Unidad de Patología Mitocondrial, CNM, Instituto de Salud Carlos III, Madrid, Spain. rmartin@isciii.es
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martín-Jiménez
authors.forename: Elena
authors.initials: E
authors.lastname: Martín-Hernández
authors.forename: Ana
authors.initials: A
authors.lastname: Cabello
authors.forename: María Teresa
authors.initials: MT
authors.lastname: García-Silva
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008564:Membrane Potentials; D028361:Mitochondrial Diseases; D051336:Mitochondrial Membranes / Q000502:physiology; D032342:Muscle Cells / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D017354:Point Mutation; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu; D017382:Reactive Oxygen Species; D012313:RNA; D000255:Adenosine Triphosphate