UCLA

X linked progressive cone-rod dystrophy (COD) is a retinal disease primarily affecting the cone photoreceptors. The disease is genetically heterogeneous and two loci, COD1 (Xp21.1-11.4) and COD2 (Xq27.2-28), have been previously identified. COD1 was recently shown to be caused by mutations in RPGR exon ORF15 (Xp21.1), the gene that is also responsible for RP3 type retinitis pigmentosa. In this study, we performed a linkage study to map the disease gene in a large Finnish family with X linked cone-rod dystrophy, using a panel of 39 X chromosomal markers. Several recombinations between the disease gene and markers in the Xp21.1-p11.4 region have excluded COD1 as a candidate locus in this family. Consistent with the linkage results, no mutation was detected by direct PCR sequencing of the coding region of RPGR, including exon ORF15. The COD2 locus has been also excluded as the site of the gene on the basis of negative lod score values obtained for COD2 linked markers. The disease causing gene of the studied COD family has been localised between the markers DXS10042 and DXS8060 on Xp11.4-q13.1. Positive pairwise lod scores >3 were obtained for markers DXS993, MAOB, DXS1055, and DXS1194. Since this locus is distinct from the previously identified two loci, COD1 and COD2, our results establish a new third genetic locus for X linked progressive cone-rod dystrophy and further expands our knowledge about the genetic heterogeneity underlying this disease entity.