Partial tandem duplication of mtDNA-tRNA Phe impairs mtDNA translation in late-onset mitochondrial myopathy

Paola Arzuffi, Costanza Lamperti, Erika Fernandez-Vizarra, Paola Tonin, Lucia Morandi, Massimo Zeviani

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

An 80-year-old woman (PI) has been suffering of late onset progressive weakness and wasting of lower-limb muscles, accompanied by high creatine kinase levels in blood. A muscle biopsy, performed at 63years, showed myopathic features with partial deficiency of cytochrome c oxidase. A second biopsy taken 7years later confirmed the presence of a mitochondrial myopathy but also of vacuolar degeneration and other morphological features resembling inclusion body myopathy. Her 46-year-old daughter (PII) and 50-year-old son (PIII) are clinically normal, but the creatine kinase levels were moderately elevated and the EMG was consistently myopathic in both. Analysis of mitochondrial DNA sequence revealed in all three patients a novel, homoplasmic 15bp tandem duplication adjacent to the 5' end of mitochondrial tRNA Phe gene, encompassing the first 11 nucleotides of this gene and the four terminal nucleotides of the adjacent D-loop region. Both mutant fibroblasts and cybrids showed low oxygen consumption rate, reduced mitochondrial protein synthesis, and decreased mitochondrial tRNA Phe amount. These findings are consistent with an unconventional pathogenic mechanism causing the tandem duplication to interfere with the maturation of the mitochondrial tRNA Phe transcript.

Original languageEnglish
Pages (from-to)50-55
Number of pages6
JournalNeuromuscular Disorders
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Mitochondrial Myopathies
RNA, Transfer, Phe
Mitochondrial DNA
Creatine Kinase
Nuclear Family
Nucleotides
Cytochrome-c Oxidase Deficiency
Biopsy
Muscles
Mitochondrial Proteins
Inclusion Bodies
Muscular Diseases
DNA Sequence Analysis
Oxygen Consumption
Genes
Lower Extremity
Fibroblasts

Keywords

  • Cytochrome c oxidase
  • Mitochondrial myopathy
  • MtDNA
  • MtDNA mutation
  • MtDNA translation
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology

Cite this

Partial tandem duplication of mtDNA-tRNA Phe impairs mtDNA translation in late-onset mitochondrial myopathy. / Arzuffi, Paola; Lamperti, Costanza; Fernandez-Vizarra, Erika; Tonin, Paola; Morandi, Lucia; Zeviani, Massimo.

In: Neuromuscular Disorders, Vol. 22, No. 1, 01.2012, p. 50-55.

Research output: Contribution to journalArticle

Arzuffi, Paola ; Lamperti, Costanza ; Fernandez-Vizarra, Erika ; Tonin, Paola ; Morandi, Lucia ; Zeviani, Massimo. / Partial tandem duplication of mtDNA-tRNA Phe impairs mtDNA translation in late-onset mitochondrial myopathy. In: Neuromuscular Disorders. 2012 ; Vol. 22, No. 1. pp. 50-55.
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