Sex Distributions in the Most Frequent Autosomal Genetic Causes of Retinitis Pigmentosa

The purpose of this study was to explore whether sex imbalances are detectable in the most frequent genetic causes of retinitis pigmentosa (RP).

Databases from centers in three countries (Moorfields Eye Hospital, London; Hospital for Sick Children, Toronto; and Australian Inherited Retinal Disease Registry, Perth, Australia) were searched, quantifying numbers of male and female patients with disease attributed to variants in the six most frequently involved autosomal RP genes. Proportions of female patients (with 95% confidence intervals [CIs]) were calculated for each gene. Two-tailed binomial testing was performed (Bonferroni corrected threshold, P = 0.008) to investigate whether proportions differed significantly from an underlying male:female ratio of 1:1. For genes where the 95% CI did not include 50%, sex distributions were also explored in previously published cohorts.

Our search yielded 1454 patients with disease attributable to variants in USH2A (n = 550), RP1 (n = 277), RHO (n = 246), PRPF31 (n = 158), EYS (n = 124), and MYO7A (n = 99). Proportions of female patients (95% CI) for each gene were 46.2% (42.0-50.5%), 49.5% (43.4-55.5%), 55.3% (48.8-61.6%), 63.9% (55.9-71.3%), 39.5% (31.0-48.7%), and 42.4% (32.7-52.8%), respectively. The 95% CI did not include 50% for PRPF31 and EYS; binomial testing revealed P values of 6.24 × 10-4 and 0.025, respectively. Combining with data extracted from previously published cohorts yielded P values of 1.62 × 10-6 and 0.0084, respectively.

We observed a significant preponderance of female patients for PRPF31-associated RP and a preponderance of male patients in those with EYS-associated RP. Our findings suggest that sex is likely to be a modifier affecting penetrance in PRPF31-associated disease and might act in the opposite direction in disease associated with EYS.