X-linked retinitis pigmentosa associated with a 2-base pair insertion in codon 99 of the RP3 gene RPGR

Background: Mutations in the RPGR gene at the RP3 locus have been found to cause X-linked retinitis pigmentosa in some families. Objectives: To identify a previously undescribed 2-base pair insertion in codon 99 of the RPGR gene and to describe the phenotype in a well- characterized family with X-linked retinitis pigmentosa. Design: Case reports with clinical features, fluorescein angiography, kinetic perimetry, electrophysiological studies, and molecular genetics. Selling: University medical centers. Patients: Eight members of the family were screened for the codon 99 insertion in the RPGR gene. Results: Three affected males were found to be hemizygous for the 2- base pair insertion; 2 carriers were heterozygous. This insertion creates a frameshift that would be expected to cause a premature arrest of translation after only 132 amino acids (683 amino acids less than the normal protein). The affected males had typical retinitis pigmentosa with visual field contraction and abnormal findings on electroretinograms with little to no rod activity, profoundly subnormal residual cone responses to single flash and 30-Hz flicker stimuli, and prolonged b-wave implicit times. The electroretinogram of a 49-year- old carrier showed amplitudes that were roughly half of normal. Carrier women did not show a tapetallike fundus reflex but showed asymmetrical patchy pigmentary disturbances consistent with lyonization. Conclusion: A frameshifting 2-base pair insertion at codon 99 of the RPGR gene produced typical retinitis pigmentosa and carrier findings (but no tapetallike reflex) in this family.