An autosomal locus predisposing to multiple deletions of mtDNA on chromosome 3p

Am J Hum Genet. 1996 Apr;58(4):763-9.


Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more respiratory-chain enzymes carrying mtDNA-encoded subunits. The pattern of inheritance indicates a nuclear gene defect predisposing to secondary mtDNA deletions. Recently, in one Finnish family, we assigned an adPEO locus to chromosome 10q 23.3-24.3 but also excluded linkage to this same locus in two Italian adPEO families with a phenotype closely resembling the Finnish one. We applied a random mapping approach to informative non-10q-linked Italian families to assign the second locus for adPEO and found strong evidence for linkage on chromosome 3p 14.1-21.2 in three Italian families, with a maximum two-point lod score of 4.62 at a recombination fraction of .0. However, in three additional families, linkage to the same chromosomal region was clearly absent, indicating further genetic complexity of the adPEO trait.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 3*
  • DNA, Mitochondrial / genetics*
  • Female
  • Genotype
  • Humans
  • Italy
  • Male
  • Ophthalmoplegia, Chronic Progressive External / genetics*
  • Pedigree
  • Sequence Deletion / genetics*


  • DNA, Mitochondrial

Grant support