PHENOTYPE OF AN X-LINKED RETINITIS-PIGMENTOSA FAMILY WITH A NOVEL SPLICE DEFECT IN THE RPGR GENE

PURPOSE. To assess the clinical phenotype in a Swedish family with X-l inked retinitis pigmentosa (XLRP) resulting from a novel splice defect in the RPGR gene. METHODS. RPGR mutation analysis was performed in on e family with XLRP, and several individuals from the family were exami ned clinically. RESULTS. The causative mutation in the family was demo nstrared to be a single base-pair change at the splice donor site in i ntron 7 that resulted in skipping of the complete exon 7 in the mature RPGR transcript. The aberrant mRNA is predicted to produce an RPGR pr otein with an in-frame deletion of 53 amino acids, corresponding to an RCC1-homology repeat. Clinical studies that included ophthalmological examination and full-field electroretinography showed that this splic e mutation resulted in a comparatively less severe form of RP. CONCLUS IONS. Correlation of a causative RPGR genotype with clinical findings in hemizygotes and carrier heterozygotes is an important step toward p redictive diagnosis and should assist in the development of gene-based therapies in the future.