Defective mitochondrial ATPase due to rare mtDNA m.8969G>A mutation-causing lactic acidosis, intellectual disability, and poor growth

Neurogenetics. 2018 Jan;19(1):49-53. doi: 10.1007/s10048-018-0537-9. Epub 2018 Jan 19.

Abstract

Mutations in mitochondrial ATP synthase 6 (MT-ATP6) are a frequent cause of NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) or Leigh syndromes, especially a point mutation at nucleotide position 8993. M.8969G>A is a rare MT-ATP6 mutation, previously reported only in three individuals, causing multisystem disorders with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia or IgA nephropathy. We present two siblings with the m.8969G>A mutation and a novel, substantially milder phenotype with lactic acidosis, poor growth, and intellectual disability. Our findings expand the phenotypic spectrum and show that mtDNA mutations should be taken account also with milder, stable phenotypes.

Keywords: Intellectual disability; Lactic acidosis; Mitochondrial DNA; Mitochondrial diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / complications
  • Acidosis, Lactic / genetics*
  • Adolescent
  • Child
  • DNA, Mitochondrial / genetics*
  • Female
  • Growth Disorders / complications
  • Growth Disorders / genetics*
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / genetics*
  • Male
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Pedigree
  • Phenotype
  • Point Mutation
  • Siblings

Substances

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