Sex Distributions in Non-ABCA4 Autosomal Macular Dystrophies

Abstract

Purpose We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies. Methods We searched the electronic patient records of our large inherited retinal disease cohort, quantifying numbers of males and females with the more common (non- ABCA4 ) inherited macular dystrophies (associated with BEST1 , EFEMP1 , PROM1 , PRPH2 , RP1L1 , and TIMP3 ). BEST1 cases were subdivided into typical autosomal dominant and recessive disease. For PRPH2 , only patients with variants at codons 172 or 142 were included. Recessive PROM1 and recessive RP1L1 cases were excluded because these variants give a more widespread or peripheral degeneration. The proportion of females was calculated for each condition; two-tailed binomial testing was performed. Where a significant imbalance was found, previously published cohorts were also explored. Results Of 325 patients included, numbers for BEST1 , EFEMP1 , PROM1 , PRPH2 , RP1L1 , and TIMP3 were 152, 35, 30, 50, 14, and 44, respectively. For autosomal dominant Best disease ( n = 115), there were fewer females (38%; 95% confidence interval [CI], 29–48%; P = 0.015). For EFEMP1 -associated disease ( n = 35), there were significantly more females (77%; 95% CI, 60%–90%; P = 0.0019). No significant imbalances were seen for the other genes. When pooling our cohort with previous large dominant Best disease cohorts, the proportion of females was 37% (95% CI, 31%–43%; P = 1.2 × 10 −5 ). Pooling previously published EFEMP1 -cases with ours yielded an overall female proportion of 62% (95% CI, 54%–69%; P = 0.0023). Conclusions This exploratory study found significant sex imbalances in two autosomal macular dystrophies, suggesting that sex could be a modifier. Our findings invite replication in further cohorts and the investigation of potential mechanisms.