A new mitochondrial disease associated with mitochondrial DNA heteroplasmy

Am J Hum Genet. 1990 Mar;46(3):428-33.


A variable combination of developmental delay, retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy occurred in four members of a family and was maternally transmitted. There was no histochemical evidence of mitochondrial myopathy. Blood and muscle from the patients contained two populations of mitochondrial DNA, one of which had a previously unreported restriction site for AvaI. Sequence analysis showed that this was due to a point mutation at nucleotide 8993, resulting in an amino acid change from a highly conserved leucine to arginine in subunit 6 of mitochondrial H(+)-ATPase. There was some correlation between clinical severity and the amount of mutant mitochondrial DNA in the patients; this was present in only small quantities in the blood of healthy elderly relatives in the same maternal line.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acids / genetics
  • Animals
  • Base Sequence
  • Child, Preschool
  • DNA, Mitochondrial / genetics*
  • Deoxyribonucleases, Type II Site-Specific
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondria, Muscle / enzymology
  • Mitochondria, Muscle / metabolism
  • Molecular Sequence Data
  • Muscular Diseases / enzymology
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology
  • Mutation*
  • Pedigree
  • Proton-Translocating ATPases / blood
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / metabolism


  • Amino Acids
  • DNA, Mitochondrial
  • CYCGRG-specific type II deoxyribonucleases
  • Deoxyribonucleases, Type II Site-Specific
  • Proton-Translocating ATPases