X-linked dominant cone-rod degeneration: linkage mapping of a new locus for retinitis pigmentosa (RP 15) to Xp22.13-p22.11.
Retinitis pigmentosa is the name given to a heterogeneous group of hereditary retinal degenerations characterized by progressive visual field loss, pigmentary changes of the retina, abnormal electroretinograms, and, frequently, night blindness. In this study, we investigated a family with dominant cone-rod degeneration, a variant form of retinitis pigmentosa. We used microsatellite markers to test for linkage to the disease locus and excluded all mapped autosomal loci. However, a marker from the short arm of the X chromosome, DXS989, showed 0% recombination to the disease locus, with a maximum lod (log-odds) score of 3.3. On the basis of this marker, the odds favoring X-linked dominant versus autosomal dominant inheritance are > 10(5):1. Haplotype analysis using an additional nine microsatellite markers places the disease locus in the Xp22.13-p22.11 region and excludes other X-linked disease loci causing retinal degeneration. The clinical expression of the retinal degeneration is consistent with X-linked dominant inheritance with milder, variable effects of Lyonization affecting expression in females. On the basis of these data we propose that this family has a novel form of dominant, X-linked cone-rod degeneration with the gene symbol "RP15."
McGuire
R E
RE
School of Public Health, University of Texas-Houston Health Science Center, USA.
Sullivan
L S
LS
Blanton
S H
SH
Church
M W
MW
Heckenlively
J R
JR
Daiger
S P
SP
D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D004276:DNA, Satellite / Q000032:analysis; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D010375:Pedigree; D010786:Photoreceptor Cells / Q000737:chemistry* / Q000648:ultrastructure; D012174:Retinitis Pigmentosa / Q000235:genetics*; D014960:X Chromosome
D004276:DNA, Satellite