X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60

Objective: This study describes the ophthalmic findings in two unrelated wh ite families with X-linked retinitis pigmentosa (XLRP) caused by a missense mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene. Design: Genetic screening and clinical correlation. Participants: Thirty-six families with XLRP seen by the authors were screen ed for a possible mutation in the RPGR gene to identify three affected hemi zygotes with retinitis pigmentosa and four heterozygote carriers in one fam ily and one hemizygote and one carrier in a second family. Intervention: All nine patients underwent a routine ocular examination, inc luding slit-lamp biomicroscopy and a dilated fundus examination. Goldmann v isual field kinetic perimetry, static threshold perimetry, and electroretin ography also were obtained. The DNA screening was performed on the three af fected male patients and four obligate carriers examined from one family an d the two examined patients, plus an additional male and obligate carrier, from the second family to determine the presence of any causative mutation in the RPGR gene. Main Outcome Measures: Findings on fundus examination, static threshold and kinetic perimetry, and electroretinography testing were the main outcome m easures. Results: A G-->T nucleotide change at position 238 in exon 3 of the RPGR ge ne resulting in a putative substitute of Gly-->Val at codon 60 was shown to segregate with RP in affected males and the carrier state in female hetero zygotes in these two families. The ophthalmologic findings in hemizygotes a s well as the carriers in this family were within the spectrum of findings characteristically noted in XLRP families, A tapetal-like reflex was not ob served in any of the five female carriers. Psychophysical and electrophysio logic testing on the carriers indicated that cone and rod functions were im paired equivalently. When present in the carriers, visual field restriction was most apparent in, or limited to, the superotemporal quadrant, which co rresponded to the retinal pigmentary changes that tended to occur in the in feronasal retina. Conclusions: A mutation in exon 3 of the RPGR gene, which would result in a putative glycine to valine substitution at codon 60, is associated with a severe clinical phenotype in male patients and a patchy retinopathy without a tapetal-like reflex in carrier females. In these families, heterozygote carriers showed equivalent impairment of their cone and rod function.