PHENOTYPES IN 3 SWEDISH FAMILIES WITH X-LINKED RETINITIS-PIGMENTOSA CAUSED BY DIFFERENT MUTATIONS IN THE RPGR GENE

PURPOSE: To assess the clinical phenotypes in three Swedish families;w ith X-linked retinitis pigmentosa caused by different mutations in the RPGR gene. METHODS: Three families from different parts of Sweden, in cluding nine patients with retinitis pigmentosa and six female carrier s of X-linked retinitis pigmentosa, were examined clinically. Ophthalm ologic examination included kinetic perimetry with a Goldmann perimete r using standardized objects I-4e and V-4e, dark adaptation final thre sholds with a Goldmann-Weeker adaptometer, and full field electroretin ograms. RESULTS: The clinical findings in the patients demonstrated a severe form of retinitis pigmentosa with visual handicap early in life . Patients with a microdeletion of exons 8 through 10 of the RPGR gene had a more severe phenotype compared to the patients with single-base pair mutations in the introns 10 and 13 of: the RPGR gene, resulting in splicing defects. Furthermore, heterozygous carriers in these famil ies displayed a wide spectrum of clinical features, from minor symptom s to severe visual disability. CONCLUSION: These three families show a variable clinical phenotype resulting from different mutations in the RPGR gene. A microdeletion spanning at least parts of exons 8 through 10 seems to result in a severe phenotype compared to the splice defec ts. Heterozygous carriers of X-linked retinitis pigmentosa with these specific RPGR genotypes also show a variability of the phenotype; carr iers with the microdeletion may be severely visually handicapped.