LOCALIZATION OF CSNBX (CSNB4) BETWEEN THE RETINITIS-PIGMENTOSA LOCI RP2 AND RP3 ON PROXIMAL XP

Purpose. Proximal Xp harbors many inherited retinal disorders, includi ng retinitis pigmentosa (RP) and congenital stationary night blindness , both of which display genetic heterogeneity. X-linked congenital sta tionary night blindness (CSNBX) is a nonprogressive disease causing ni ght blindness and reduced visual acuity. Distinct genetic loci have be en reported for CSNBX at Xp21.1, which is potentially allelic with the RP3 gene, and at Xp11.23, which is potentially allelic with the RP2 g ene. The study to identify the RP2 gene led to an extended study of fa milies with potentially allelic diseases that include CSNBX. Methods. Haplotype analysis of a family diagnosed with CSNBX was performed with 17 polymorphic markers on proximal Xp covering previously identified loci for CSNBX and XLRP. Two-point and multipoint lod scores were calc ulated. Results. Informative recombinations in this family define a lo cus for CSNBX (CSNB4) with flanking markers DXS556 and DXS8080 on Xp11 .4 to Xp11.3, an interval spanning approximately 5 to 6 cM. A maximum lod score of 3.2 was calculated for the locus order DXS556-1 cM-(CSNB4 -DXS993)-2 cM-DXS1201. Conclusions. The results describe a new localiz ation for CSNBX (CSNB4) between the RP2 and RP3 loci on proximal Xp. C SNB4 is not allelic with any previously reported XLRP loci; however, t he interval overlaps the locus reported to contain the cone dystrophy (COD1) gene, and both diseases are nonrecombinant with DXS993. Because mutations in the RPGR gene to date account for disease in only a smal l proportion of RP3 families, the possibility that this new locus (CSN B4) also segregates with an as yet unidentified XLRP locus cannot be e xcluded.