X-inactivation pattern in multiple tissues from two Leber's hereditary optic neuropathy (LHON) patients

Elena Pegoraro, Andrea Vettori, Maria L. Valentino, Annamaria Molon, Maria L. Mostacciuolo, Neil Howell, Valerio Carelli

Research output: Contribution to journalArticlepeer-review


The more frequent manifestation of ophthalmological abnormalities in males, relative to females, is an unexplained feature of Leber's hereditary optic neuropathy (LHON) that suggests an X-linked modifying gene acting in concert with the pathogenic LHON mitochondrial DNA (mtDNA) mutation. In addition, segregation analysis of the optic neuropathy in LHON pedigrees was compatible with the presence of a recessive-modifying gene on chromosome X. According to this two-locus model, females would be affected only if homozygous or if they were susceptible to skewed X-inactivation. Attempts both to localize the putative LHON-modifying gene by linkage analysis and to find an excess of skewed X-inactivation in affected females were unsuccessful, although the inactivation pattern was only studied in DNA isolated from blood cells. We had the opportunity to analyze a wide range of tissues at autopsy, including the optic nerves and the retina, from two LHON female patients. We found no evidence of skewed X-inactivation in the affected tissues, thus weakening further the hypothesized involvement of a specific X chromosome locus in the pathophysiological expression of LHON.

Original languageEnglish
Pages (from-to)37-40
Number of pages4
JournalAmerican Journal of Medical Genetics
Volume119 A
Issue number1
Publication statusPublished - May 15 2003


  • LHON
  • Mitochondria
  • X-inactivation

ASJC Scopus subject areas

  • Genetics(clinical)


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