Evidence for a novel X-linked modifier locus for leber hereditary optic neuropathy

Suma P. Shankar, John H. Fingert, Valerio Carelli, Maria L. Valentino, Terri M. King, Stephen P. Daiger, Solange R. Salomao, Adriana Berezovsky, Rubens Belfort, Terri A. Braun, Val C. Sheffield, Alfredo A. Sadun, Edwin M. Stone

Research output: Contribution to journalArticlepeer-review


Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited blinding disease caused by missense mutations in the mitochondrial DNA (mtDNA). However, incomplete penetrance and a predominance of male patients presenting with vision loss suggest that modifying factors play an important role in the development of the disease. Evidence from several studies suggests that both nuclear modifier genes and environmental factors may be necessary to trigger the optic neuropathy in individuals harboring an LHON-causing mtDNA mutation. Recently, an optic neuropathy susceptibility locus at Xp21-Xq21 has been reported. In this study, we performed X-chromosomal linkage analysis in a large Brazilian family harboring a homoplasmic G11778A mtDNA mutation on a haplogroup J background. We report the identification of a novel LHON susceptibility locus on chromosome Xq25-27.2, with multipoint non-parametric linkage scores of > 5.00 (P = 0.005) and a maximum two-point non-parametric linkage score of 10.12, (P = 0.003) for marker DXS984 (Xq27.1). These results suggest genetic heterogeneity for X-linked modifiers of LHON.

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalOphthalmic Genetics
Issue number1
Publication statusPublished - Mar 2008


  • Leber hereditary optic neuropathy
  • LHON
  • Modifier gene
  • Optic atrophy
  • X-linked modifiers locus

ASJC Scopus subject areas

  • Ophthalmology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)


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