A second family with X–linked retinitis pigmentosa mapping to the RP24 locus

Abstract

Abstract: : Purpose: To fine map the locus of a family with X–linked retinitis pigmentosa (RP) not associated to RP2 and RP3 Methods: A 3–generation family with 5 affected, 2 non affected males, and 2 obligatory female carriers was investigated after informed consent. Linkage analysis was performed using the X–linked microsatellites from the ABI linkage mapping set 2.5. PCR products were resolved on an ABI3100 machine and scored with the GeneMapper program. Lod score evaluation was performed with MLINK version 5.2 using equal allele frequency and a new mutation rate of 10^–4. Results: The phenotype of the hemizygotes was characterized by typical retinitis pigmentosa and early involvement of the macula. Interestingly the 2 female obligate carriers were asymptomatic and had normal full field scotopic and photopic ERGs. Linkage analysis revealed positive Lod scores for markers DXS1205 to DXS1073 (max Lod score: 2.61 for marker DXS1205 and DXS8043). Haplotype analysis shows a recombination event between DXS1211 and DXS1205 thus setting the proximal boundary somewhere between these 2 markers. Conclusions: Our data confirm the existence of an RP locus at Xq26–27. This region contains several candidate genes. Additional family members are currently being recruted and positional cloning is under way.

Keywords: genetics • linkage analysis • retinitis