Mutations in the candidate gene for Norrie disease.

Recently, we and others have isolated a candidate gene for X linked Norrie disease (ND) which was found to be deleted or disrupted in several patients. As a prerequisite for the identification of point mutations in the ND gene we have established the exon-intron structure of this gene. In 17 unrelated patients and 15 controls, PCR products derived from the promoter region, exons 1 and 2 as well as the coding part of exon 3 were analysed with the single strand conformation polymorphism (SSCP) technique. In 12 patients altered PCR fragments were detected which were studied in detail by direct sequencing. Eleven different mutations were found, and all but one are likely to give rise to significant structural changes in the predicted protein. These findings, and the absence of functionally relevant base changes in healthy controls, emphasize the causal role of this candidate gene in Norrie disease and pave the way for reliable diagnosis and carrier detection.