Phenotype in two families with RP3 associated with RPGR mutations

To describe the phenotype of three patients and two carriers from two families with mutations in the RPGR gene. The genotypes (a 75-kb deletion on the X chromosome spanning the RPGR gene and the first exon of the SRPX gene, and a stop mutation (G52X) in the RPGR gene) have been reported previously.

A clinical examination including Goldmann perimetry, full-field electroretinography (ERG), dark adaptometry, and dark- and light-adapted two-color threshold (500-nm cut-off, 600-nm cut-on filter) perimetry was performed in all patients and one carrier. The second carrier was only examined clinically.

All affected males presented with a marked decrease in visual acuity of 0.3 to 0.5 at the age of 17-22.5 years, and a typical fundus appearance. The stop mutation (G52X) appeared to be associated with a more pronounced bone spicule formation compared to the deletion of the entire RPR gene and the first exon of the SRPX gene. The kinetic visual fields were constricted to < 20 degrees eccentricity, in part with a residual island in the temporal field. Using two-color dark-adapted threshold perimetry, rod function was more reduced than cone function. The ERG was extinguished. The carrier with the stop mutation showed sectorial peripheral bone spicules and ERG changes typical of carriers of XLRP. The carrier with the deletion had no visual complaints, full visual acuity, and only minimal peripheral retinal changes. Goldmann perimetry showed minor peripheral defects with small targets. ERG amplitudes were reduced below the 10th percentile of normals, without selective loss in rods or cones. The scotopic (rod) sensitivity loss at 500 nm was more pronounced than the photopic (cone) sensitivity loss at 600 nm. Neither of the two carriers showed a tapetal reflex.

The affected males of the two families with RPGR mutations already exhibited retinitis pigmentosa with severe impairment of the rod and cone system during their second decade of life. The degree of bone spicules differed between the two families. Psychophysics detected a slightly more pronounced affection of the rod system compared to the cone system in both the hemizygous males and the carrier with the deletion of the RPGR gene and the first exon of the SRPX gene. Psychophysics disclosed mild progression of the disease in the carrier underlining the potential of the method in monitoring the disease course. As in most other reported phenotypes of RPGR mutations, no tapetal reflex was found in the carriers.