HETEROGENEITY ANALYSIS IN 40 X-LINKED RETINITIS-PIGMENTOSA FAMILIES

Analysis of genetic heterogeneity in 40 kindreds with X-linked retinit is pigmentosa (XLRP), with 20 polymorphic markers, showed that signifi cant heterogeneity is present (P=.001) and that 56% of kindreds are of RP3 type and that 26% are of RP2 type. The location of the RP3 locus was found to be 0.4 cM distal to OTC in the Xp21.1 region, and that of the RP2 locus was 6.5 cM proximal to DXS7 in Xp11.2-p11.3. Bayesian p robabilities of linkage to RP2, RP3, or to neither locus were calculat ed. This showed that 20 of 40 kindreds could be assigned to one or the other locus, with a probability >.70 (14 kindreds with RP3 and 6 kind reds with RP2 disease). A further three kindreds were found to be unli nked to either locus, with a probability >.8. The remaining 17 kindred s could not be classified unambiguously. This highlights the difficult y of classifying families in the presence of genetic heterogeneity, wh ere the two loci are separated by an estimated 16 cM.