X-inactivation patterns in female Leber's hereditary optic neuropathy patients do not support a strong X-linked determinant

Elena Pegoraro, Valerio Carelli, Massimo Zeviani, Pietro Cortelli, Pasquale Montagna, Piero Barboni, Corrado Angelini, Eric P. Hoffman

Research output: Contribution to journalArticlepeer-review


Leber's hereditary optic neuropathy (LHON) accounts for about 3% of the cases of blindness in young adult males. The underlying mitochondrial pathogenesis of LHON has been well studied, with specific mitochondrial DNA (mtDNA) mutations of structural genes described and well characterized. However, enigmatic aspects of the disease are not explained by mutation data, such as the higher proportion of affected males, the later onset of the disease in females, and the presence of unaffected individuals with a high proportion of mutant mtDNA. A hypothesis which has been put forward to explain the unusual disease expression is a dual model of mtDNA and X-linked nuclear gene inheritance. If a nuclear X-linked modifier gene influences the expression of the mitochondrial-linked mutant gene then the affected females should be either homozygous for the nuclear determinant, or if heterozygous, lyonization should favor the mutant X. In order to determine if an X-linked gent predisposes to LHON phenotype we studied X-inactivation patterns in 35 females with known mtDNA mutations from 10 LHON pedigrees. Our results do not support a strong X-linked determinant in LHON cause: 2 of the 10 (20%) manifesting carriers showed skewing of X-inactivation, as did 3 of the 25 (12%) nonmanifesting carriers.

Original languageEnglish
Pages (from-to)356-362
Number of pages7
JournalAmerican Journal of Medical Genetics
Issue number4
Publication statusPublished - Feb 2 1996


  • Leber's hereditary optic neuropathy
  • mitochondrial genetics
  • X-inactivation
  • X-linked inheritance

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)
  • Neuropsychology and Physiological Psychology


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