Germ-line deletions of mtDNA in mitochondrial myopathy

Am J Hum Genet. 1991 Apr;48(4):649-53.


mtDNA encodes subunits of the electron transport chain and is exclusively maternally inherited in mammals. It has been suggested that mtDNA might be the site of some of the mutations causing a group of human disorders called the "mitochondrial myopathies," because these may both be (1) accompanied by defects in the electron transport chain and (2) display a maternal pattern of inheritance. However, all of the deletions and duplications of mtDNA which occur in these patients have been sporadic, apart from families in whom affected members all carry different deletions suggesting a mutant autosomal dominantly inherited nuclear gene with de novo deletions in each individual. We present the first evidence for the presence of deleted mtDNAs in the germ line in these disorders. The patient carries a higher level of deleted mtDNAs than do his relatives, corresponding to severity of symptoms and consistent with a predicted dosage effect. "Selfishness" of deleted mtDNAs is probably one of the factors over and above random segregation of a small number of "founder" mtDNAs (the bottleneck hypothesis) which may be invoked to explain the usual distribution of mtDNAs in different tissues of patients with mtDNA deletions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Chromosome Deletion*
  • DNA, Mitochondrial / chemistry*
  • Germ Cells / metabolism*
  • Humans
  • Kearns-Sayre Syndrome / genetics*
  • Male
  • Mitochondria, Muscle / pathology*
  • Polymerase Chain Reaction


  • DNA, Mitochondrial