Phenotype of Heterozygotes with Mutations in the ORF 15 (Open Reading Frame 15) of RPGR

Abstract

Abstract: : Purpose: To document the clinical signs, symptoms and electrophysiological findings in subjects known to be heterozygous for mutations in ORF 15 of the RPGR gene, which causes X-linked retinitis pigmentosa. Methods: Known heterozygotes from families with X-linked retinitis pigmentosa, in whom a mutation in ORF 15 of RPGR had been ascertained, were invited to attend for examination. Those who agreed completed a questionnaire detailing past history and symptoms and underwent a complete clinical examination. ERG and pattern ERG testing was performed to incorporate ICSEV standards. Results: 27 subjects, ranging in age from 20 - 71 years, were recruited. Nyctalopia was reported by 67%, 33% had a symptomatic field defect, and 30% had vision of 6/18 or worse in at least one eye. 26% of subjects reported no visual deficit. Relevant fundal abnormalities were present in 92% of subjects: bone spicules in 48%, tapetal reflex only in 44%. Some abnormality in full field ERG was present all of the subjects tested, ranging from severe dysfunction in rod and cone systems to mild cone or rod system dysfunction only. Rods and cones were affected to a similar degree in 59%, cone dysfunction was greater in 23% and rod system dysfunction predominated in 18%. Macular dysfunction was present in 86%. Conclusions: All volunteer subjects examined, heterozygous for mutation in ORF 15, had abnormal electrophysiology. There was marked heterogeneity of the findings observed, possibly due to random X chromosome inactivation, but both rod and cone systems were affected in the majority of subjects.

Keywords: retinal degenerations: hereditary • mutations • electroretinography: clinical