■我们试图探索性别失衡在几种常染色体遗传性黄斑营养不良中是否明显。
■我们搜索了大型遗传性视网膜疾病队列的电子病历,量化男性和女性患有更常见(非ABCA4)遗传性黄斑营养不良(与BEST1、EFEMP1、PROM1、PRPH2、RP1L1和TIMP3相关)的数量。BEST1病例分为典型的常染色体显性和隐性疾病。对于PRPH2,仅包括在密码子172或142处具有变体的患者。隐性PROM1和隐性RP1L1病例被排除,因为这些变异会导致更广泛的或周围的变性。计算每种情况下女性的比例;进行双尾二项测试。在发现显著不平衡的地方,以前发表的队列也进行了探索。
■在包括的325名患者中,BEST1,EFEMP1,PROM1,PRPH2,RP1L1和TIMP3的编号分别为152,35,30,50,14和44。对于常染色体显性遗传的最佳疾病(n=115),女性较少(38%;95%置信区间[CI],29-48%;P=0.015)。对于EFEMP1相关疾病(n=35),女性明显更多(77%;95%CI,60%-90%;P=0.0019).其他基因没有发现明显的失衡。当将我们的队列与以前的大型显性最佳疾病队列合并时,女性比例为37%(95%CI,31%-43%;P=1.2×10-5)。将先前发表的EFEMP1病例与我们的病例合并后,女性总比例为62%(95%CI,54%-69%;P=0.0023)。
■这项探索性研究发现两个常染色体黄斑营养不良患者存在显著的性别失衡,暗示性可能是一种修饰。我们的发现邀请在进一步的队列中复制和潜在机制的研究。
UNASSIGNED: We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.