title: Optic atrophy in Leber hereditary optic neuroretinopathy is probably determined by an X-chromosomal gene closely linked to DXS7.
abstract: Leber hereditary optic neuroretinopathy (LHON) is a maternally inherited disease, probably transmitted by mutations in mtDNA. The variation in the clinical expression of the disease among family members has remained unexplained, but pedigree data suggest an involvement of an X-chromosomal factor. We have studied genetic linkage of the liability to develop optic atrophy to 15 polymorphic markers on the X chromosome in six pedigrees with LHON. The results show evidence of linkage to the locus DXS7 on the proximal Xp. Tight linkage to the other marker loci was excluded. Multipoint linkage analysis placed the liability locus at DXS7 with a maximum lod score (Zmax) of 2.48 at a recombination fraction (theta) of .0 and with a Zmax - 1 support interval theta = .09 distal to theta = .07 proximal of DXS7. No evidence of heterogeneity was found among different types of families, with or without a known mtDNA mutation associated with LHON.
authors.affiliation: Department of Medical Genetics, University of Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Vilkki
authors.forename: J
authors.initials: J
authors.lastname: Ott
authors.forename: M L
authors.initials: ML
authors.lastname: Savontaus
authors.forename: P
authors.initials: P
authors.lastname: Aula
authors.forename: E K
authors.initials: EK
authors.lastname: Nikoskelainen
mesh_terms: D000328:Adult; D002874:Chromosome Mapping; D004272:DNA, Mitochondrial / Q000032:analysis*; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009154:Mutation; D015418:Optic Atrophies, Hereditary / Q000175:diagnosis*; D010375:Pedigree; D011995:Recombination, Genetic; D014960:X Chromosome / Q000648:ultrastructure*
chemical_list: D004272:DNA, Mitochondrial