title: Exercise intolerance associated with a novel 8300T > C mutation in mitochondrial transfer RNAlys.
abstract: Mutations in the mitochondrial genome contribute to the pathophysiology of many neuromuscular diseases. Recently there has been an increased appreciation of the role of mitochondrial DNA (mtDNA) mutations in the etiology of exercise intolerance. Using TTGE (temporal temperature-gradient gel electrophoresis) and sequence analyses of the entire mitochondrial genome, we identified a novel heteroplasmic mutation (8300T > C) in the tRNAlys gene (MTTK) from a patient with unexplained exercise intolerance. The mutation was present in blood, hair, and muscle, with the highest percentage of heteroplasmy found in muscle. The results of muscle respiratory chain enzyme analysis are consistent with tRNA mutation. These data suggest that this novel mutation is yet another mtDNA mutation associated with muscle disease and should be considered in patients with similar symptoms.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gambello
authors.forename: Ren-Kui
authors.initials: RK
authors.lastname: Bai
authors.forename: Tian-Jian
authors.initials: TJ
authors.lastname: Chen
authors.forename: Mazen
authors.initials: M
authors.lastname: Dimachkie
authors.forename: Lee-Jun C
authors.initials: LJ
authors.lastname: Wong
mesh_terms: D000328:Adult; D001483:Base Sequence; D003596:Cytosine; D004272:DNA, Mitochondrial / Q000235:genetics; D004579:Electron Transport / Q000502:physiology; D017079:Exercise Tolerance / Q000235:genetics* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000503:physiopathology; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics* / Q000502:physiology; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012357:RNA, Transfer, Lys / Q000235:genetics*; D013941:Thymine
chemical_list: D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012357:RNA, Transfer, Lys; D012313:RNA; D003596:Cytosine; D013941:Thymine