title: Evidence for a novel x-linked modifier locus for leber hereditary optic neuropathy.
abstract: 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.
authors: Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, USA.
authors: Suma P
authors: SP
authors: Shankar
authors: John H
authors: JH
authors: Fingert
authors: Valerio
authors: V
authors: Carelli
authors: Maria L
authors: ML
authors: Valentino
authors: Terri M
authors: TM
authors: King
authors: Stephen P
authors: SP
authors: Daiger
authors: Solange R
authors: SR
authors: Salomao
authors: Adriana
authors: A
authors: Berezovsky
authors: Rubens
authors: R
authors: Belfort
authors: Terri A
authors: TA
authors: Braun
authors: Val C
authors: VC
authors: Sheffield
authors: Alfredo A
authors: AA
authors: Sadun
authors: Edwin M
authors: EM
authors: Stone
mesh_terms: D001938:Brazil; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree
chemical_list: D004272:DNA, Mitochondrial