Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy.
Leber hereditary optic neuropathy (LHON) is associated with mutations of mtDNA, but two features of LHON pedigrees are not explicable solely on the basis of mitochondrial inheritance. There is a large excess of affected males, and not all males at risk develop the disease. These observations could be explained by the existence of an X-linked visual loss susceptibility gene. This hypothesis was supported by linkage studies in Finland, placing the susceptibility locus at DXS7, with a maximum lod score of 2.48 at a recombination fraction of 0. Linkage studies in 1 Italian and 12 British families with LHON, analyzed either together or separately depending on the associated mtDNA mutation, have excluded the presence of such a locus from an interval of about 30 cM around DXS7 in these kindreds, with a total lod score of -26.51 at a recombination fraction of 0.
Sweeney
M G
MG
University Department of Clinical Neurology, Institute of Neurology, Queen Square, London, England.
Davis
M B
MB
Lashwood
A
A
Brockington
M
M
Toscano
A
A
Harding
A E
AE
D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000097:blood; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D004739:England; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D015418:Optic Atrophies, Hereditary / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014786:Vision Disorders / Q000209:etiology / Q000235:genetics*; D014960:X Chromosome
D004272:DNA, Mitochondrial; D009838:Oligodeoxyribonucleotides; D004247:DNA