Localization of the gene for X-linked recessive type of retinitis pigmentosa (XLRP) to Xp21 by linkage analysis.

The X-linked recessive type of retinitis pigmentosa (XLRP) causes progressive night blindness, visual field constriction, and eventual blindness in affected males by the third or fourth decade of life. The biochemical basis of the disease is unknown, and prenatal diagnosis and definitive carrier diagnosis remain elusive. Heterogeneity in XLRP has been suggested by linkage studies of families affected with XLRP and by phenotypic differences observed in female carriers. Localization of XLRP near Xp11.3 has been suggested by close linkage to an RFLP at the locus DXS7 (Xp11.3) detected by probe L1.28. In other studies a locus for XLRP with metallic sheen has been linked to the ornithine transcarbamylase (OTC) locus mapping to the Xp21 region. In this study, by linkage analysis using seven RFLP markers between Xp21 and Xcen, we examined four families with multiple affected individuals. Close linkage was found between XLRP and polymorphic sites OTC (theta = .06 with lod 5.69), DXS84 (theta = .05 with lod 4.08), and DXS206 (theta = .06 with lod 2.56), defined by probes OTC, 754, and XJ, respectively. The close linkage of OTC, 754, and XJ to XLRP localizes the XLRP locus to the Xp21 region. Data from recombinations in three of four families place the locus above L1.28 and below the Duchenne muscular dystrophy (DMD) gene, consistent with an Xp21 localization. In one family, however, one affected male revealed a crossover between XLRP and all DNA markers, except for the more distal DXS28 (C7), while his brother is recombined for this marker (C7) and not other, more proximal markers. This suggests that in this family the XLRP mutation maps near DXS28 and above the DMD locus.