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In addition, segregation analysis of the optic neuropathy in LHON pedigrees was compatible with the presence of a recessive\u2010modifying gene on chromosome X. According to this two\u2010locus model, females would be affected only if homozygous or if they were susceptible to skewed X\u2010inactivation. Attempts both to localize the putative LHON\u2010modifying gene by linkage analysis and to find an excess of skewed X\u2010inactivation 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\u2010inactivation in the affected tissues, thus weakening further the hypothesized involvement of a specific X chromosome locus in the pathophysiological expression of LHON. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.10211","type":"journal-article","created":{"date-parts":[[2003,4,17]],"date-time":"2003-04-17T10:01:57Z","timestamp":1050573717000},"page":"37-40","source":"Crossref","is-referenced-by-count":16,"title":["X\u2010inactivation pattern in multiple tissues from two leber's hereditary optic neuropathy (LHON) patients"],"prefix":"10.1002","volume":"119A","author":[{"given":"Elena","family":"Pegoraro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Vettori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria 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