Remapping of the RP15 locus for X-linked cone-rod degeneration to Xp11.4-p21.1, and identification of a de novo insertion in the RPGR exon ORF15

X-linked forms of retinitis pigmentosa (XLRP) are among the most severe, be cause of their early onset, often leading to significant vision loss before the 4th decade. Previously, the RP15 locus was assigned to Xp22, by linkag e analysis of a single pedigree with "X-linked dominant cone-rod degenerati on." After clinical reevaluation of a female in this pedigree identified he r as affected, we remapped the disease to a 19.5-cM interval (DXS1219-DXS99 3) at Xp11.4-p21.1. This new interval overlapped both RP3 (RPGR) and COD1. Sequencing of the previously published exons of RPGR revealed no mutations, but a de novo insertion was detected in the new RPGR exon, ORF15. The iden tification of an RPGR mutation in a family with a severe form of cone and r od degeneration suggests that RPGR mutations may encompass a broader phenot ypic spectrum than has previously been recognized in "typical" retinitis pi gmentosa.