Two new mutations in the MTATP6 gene associated with Leigh syndrome

Neuropediatrics. 2005 Oct;36(5):314-8. doi: 10.1055/s-2005-872845.


In this study we have analyzed the mtDNA encoded ATPase 6 and 8 genes ( MTATP6 and MTATP8) in two children with Leigh syndrome (LS) and reduced Mg (2+) ATPase activity in muscle mitochondria. In patient 1, with a mild and reversible phenotype, mutational analysis revealed a heteroplasmic T --> C mutation at nt position 9185 (T9185C) in the MTATP6. The mutation resulted in substitution of a highly conserved leucine to proline at codon 220. The proportion of the mutation was > 97 % in the patient's blood and muscle and 85 % in blood of his asymptomatic mother. Patient 2, with severe clinical phenotype and death at 2 years of age, exhibited a novel heteroplasmic T9191C missense mutation in the MTATP6, which converted a highly conserved leucine to a proline at position 222 of the polypeptide. The proportion of the mutation was 90 % in fibroblasts and 94 % muscle tissue. This mutation was absent in the patient's parents and sister suggesting that the mutation was de novo. Our findings expand the spectrum of mutations causing LS and emphasize the role of MTATP6 gene mutations in pathogenesis of LS.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Sequence / physiology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis / methods
  • DNA, Mitochondrial / genetics
  • Humans
  • Leigh Disease / genetics*
  • Leigh Disease / physiopathology
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Mutation*
  • Respiration


  • DNA, Mitochondrial
  • MT-ATP6 protein, human
  • Mitochondrial Proton-Translocating ATPases