The RP2 Phenotype and Pathogenetic Correlations in X-Linked Retinitis Pigmentosa

Abstract

Purpose: : To assess the phenotype of X-linked retinitis pigmentosa (XLRP) patients with RP2 mutations and correlate the findings with their genotype.

Methods: : Over 600 XLRP patients and carriers were screened over ten years for RP2 mutations. Twenty-five RP2 patients were evaluated clinically with standardized electroretinography (ERG), Goldmann visual fields, and ocular examinations. In addition, cases from the literature were used to augment genotype-phenotype correlations.

Results: : In our male cohort under the age of 12 years: 10/11 (91%) patients had macular pathology and 10/11 (91%) had visual acuities worse than 20/50. Two males from different families (ages 8 and 12) displayed a choroideremia-like fundus, and 9/11 (82%) of male patients were myopic with a mean error of -7.97D. Of patients with ERGs, 9/10 (90%) demonstrated severe rod-cone dysfunction. All three female carriers had macular atrophy in one or both eyes and were myopic (mean -6.23 D). We identified four novel RP2 mutations. All nine nonsense and five of seven missense mutations (71%) resulted in severe clinical presentations.

Conclusions: : Screening of the RP2 gene should be prioritized in patients less than 16 years of age characterized by X-linked inheritance, decreased BCVA (e.g.,>20/40), high myopia, and early-onset macular atrophy. Patients exhibiting a choroideremia-like fundus appearance and who do not have disease-causing mutations in the choroideremia gene (CHM) should be screened for variations in RP2. We believe that alterations in function play a significant role in RP2-associated disease pathogenesis.

Keywords: retinal degenerations: hereditary • gene/expression • genetics