A late-onset mitochondrial myopathy is associated with a novel mitochondrial DNA (mtDNA) point mutation in the tRNA(Trp) gene.

Abstract

We detected a novel pathogenic mutation, a G-->A transition at position 5521 of mitochondrial tRNA(Trp) gene, in association with familial late-onset mitochondrial myopathy. The mutation was detected in muscle but not in leukocytes from the family's proband. Morphological and biochemical studies documented a severe defect of muscle cytochrome c oxidase (COX) activity. RFLP analysis of single muscle fibers demonstrated segregation of higher percentages of mutated genomes in COX-negative ragged red fibres compared with normal fibers. A predominant impairment in synthesis of subunits I and III of complex IV due to their highest relative content of tryptophane might explain the greater susceptibility of complex IV to the pathogenic effect of this mutation. A progressive accumulation of mutated genomes in muscle can account for the late onset of symptoms observed in affected members.

• Authors: G Silvestri, M Rana, A DiMuzio, A Uncini, P Tonali, S Servidei
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 8 Issue 5 Pg. 291-5 (Jun 1998) ISSN: 0960-8966 [Print] England
• PMID: 9673981 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Mitochondrial
• RNA, Transfer, Trp
• Electron Transport Complex IV

Topics

• Aged
• DNA, Mitochondrial (genetics)
• Electromyography
• Electron Transport Complex IV (genetics, metabolism)
• Humans
• Male
• Mitochondrial Myopathies (genetics, pathology, physiopathology)
• Muscle, Skeletal (enzymology, pathology)
• Pedigree
• Point Mutation (genetics)
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• RNA, Transfer, Trp (genetics)