EVIDENCE FOR GENETIC-HETEROGENEITY IN X-LINKED CONGENITAL STATIONARY NIGHT BLINDNESS

X-linked congenital stationary night blindness (CSNB) is a nonprogress ive retinal disorder characterized by disturbed or absent night vision ; its clinical features may also include myopia, nystagmus, and impair ed visual acuity. X-linked CSNB is clinically heterogeneous, and it ma y also be genetically heterogeneous. We have studied 32 families with X-linked CSNB, including 11 families with the complete form of CSNB an d 21 families with the incomplete form of CSNB, to identify genetic-re combination events that would refine the location of the disease genes . Critical recombination events in the set of families with complete C SNB have localized a disease gene to the region between DXS556 and DXS 8083, in Xp11.4-p11.3. Critical recombination events in the set of fam ilies with incomplete CSNB have localized a disease gene to the region between DXS722 and DXS8023, in Xp11.23. Further analysis of the incom plete-CSNB families, by means of disease-associated-haplotype construc tion, identified 17 families, of apparent Mennonite ancestry, that sha re portions of an ancestral chromosome. Results of this analysis refin ed the location of the gene for incomplete CSNB to the region between DXS722 and DXS255, a distance of 1.2 Mb. Genetic and clinical analyses of this set of 32 families with X-linked CSNB, together with the fami ly studies reported in the literature, strongly suggest that two loci, one for complete (CSNB1) and one for incomplete (CSNB2) X-linked CSNB , can account for all reported mapping information.