Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy

Am J Hum Genet. 1996 Jul;59(1):103-8.


Pedigree analysis of British families with Leber hereditary optic neuropathy (LHON) closely fits a model in which a pathogenic mtDNA mutation interacts with an X-linked visual loss susceptibility locus (VLSL). This model predicts that 60% of affected females will show marked skewing of X inactivation. Linkage analysis in British and Italian families with genetically proven LHON has excluded the presence of such a VLSL over 169 cM of the X chromosome both when all families were analyzed together and when only families with the bp 11778 mutation were studied. Further, there was no excess skewing of X inactivation in affected females. There was no evidence for close linkage to three markers in the pseudoautosomal region of the sex chromosomes. The mechanism of incomplete penetrance and male predominance in LHON remains unclear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Mitochondrial / genetics
  • Dosage Compensation, Genetic
  • Female
  • Genetic Linkage*
  • Genetic Markers
  • Humans
  • Lod Score
  • Male
  • Models, Genetic
  • Optic Atrophies, Hereditary / genetics*
  • Pedigree
  • Polymorphism, Genetic
  • United Kingdom
  • X Chromosome / genetics*


  • DNA, Mitochondrial
  • Genetic Markers