Genetic And Clinical Study Of X–linked Retinitis Pigmentosa In A Large Spanish Family

Abstract

Abstract: : Purpose: The identification of the female carriers of X–linked RP is important for genetic counselling. Although different loci have been proposed on the short arm of the X–chromosome by linkage analysis, RP3 represents the disease locus in the majority of XLRP. A Spanish family with X–linked RP was previously studied by linkage analysis. It was possible to establish that a RP3 mutation is, most likely, segregating in this family. The aim of this work was identify the mutation in RPGR causing the disease in this family. Methods: Thirty–five members of a Spanish family with X–linked RP, spanning five generations were examined by ophthalmologic testing. Nine polymorphic markers representing nine different loci that map to the X–chromosome region Xp21.1–Xp11.3 from just distal to the RP3 locus and proximal to the RP2 locus were analysed in members of this family. Linkage analysis was carried out using the Linkage package version 5.1. We analysed the genomic sequence of RPGR gene and open reading frame 15 (ORF 15) in affected members of this family. Results: Affected males in this family reported night blindness during their teenage years, typical fundus features and abolished ERG responses. Five out of eleven carriers demonstrated fundus changes associated with XLRP. Haplotype analysis and an obligatory recombination between markers (DXS1058 to DXS6849) and the disease point to the fact that a RP3 mutation is segregating in this family. This recombination excluded a RP2 mutation as being the cause of XLRP in this family. Up to this moment we have sequenced 98% of the RPGR genomic sequence. No mutations were found segregating with the disease in this family. Conclusions: Although RP3 mutations explain the majority of X–linked RP, our results concluded that it is probably that RPGR is not the unique mutated gene in this locus.

Keywords: genetics • retinitis • retinal degenerations: hereditary