D-loop mutations in mitochondrial DNA: link with mitochondrial DNA depletion?

Hum Genet. 2002 May;110(5):479-87. doi: 10.1007/s00439-002-0708-4. Epub 2002 Apr 11.


Clinical presentation of the patients with mitochondrial DNA depletion is quite diverse and is suggestive of genetic heterogeneity. Autosomal recessive inheritance of the disease appears likely, thus implying the nuclear origin of the disease. This has been demonstrated recently in large families with neonatal presentation of the disease. Here, we report upon a family with one child having a late-onset disease associated with severe mitochondrial DNA depletion. The presence of mitochondrial alterations in the muscle of the patient's mother prompted us to extensively analyse the mitochondrial DNA in the family. We found mitochondrial DNA multiple deletions, but also three heteroplasmic point mutations of the D-loop region, two of which (T119C and T408A) affect conserved regions involved in the mtDNA replication process. These mutations were non-randomly distributed in the maternal lineage and, for one of them, among single muscle fibres. Involvement of the mitochondrial DNA in its own depletion appears therefore possible. It may act in close relationship with a hypothetical modified nuclear factor.

Publication types

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

MeSH terms

  • Age of Onset
  • Base Sequence
  • Cell Nucleus / genetics
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Extrachromosomal Inheritance
  • Female
  • Humans
  • Kidney / pathology
  • Male
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondria / pathology
  • Molecular Sequence Data
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Muscular Diseases / enzymology
  • Muscular Diseases / genetics
  • Muscular Diseases / pathology
  • Mutation / genetics*
  • Organ Specificity
  • Pedigree
  • Polymerase Chain Reaction
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Replication Origin / genetics
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism


  • DNA, Mitochondrial
  • Succinate Dehydrogenase
  • Electron Transport Complex IV