Characterizing the genotypic spectrum of retinitis pigmentosa in East Asian populations: a systematic review

Ongoing trials for retinitis pigmentosa (RP) are genotype-specific, with most trials conducted on European cohorts. Due to genetic differences across diverse ancestries and populations, these therapies may not be efficacious in East Asians. A literature search was conducted from 1966 to September 2022 for cohort studies on East Asian populations reporting on non-syndromic RP genotypes and variants. Population-weighted prevalence was used to determine the genotypes and individual variants across the entire cohort. The carrier prevalence of common variants was compared against those in Europe. A total of 12 articles describing 2,932 clinically diagnosed East Asian RP probands were included. We identified 876 variants across 54 genes. The most common genotypes included USH2A, EYS, RPGR, ABCA4, PRPF31, RHO, RP1, RP2, PDE6B and SNRNP200, with USH2A as the most common (17.1%). Overall, 60.5% of probands with clinically relevant variants were found to have one of the genotypes above, with 543/876 (62.0%) of the variants occurring in these genes. The most frequently reported variant was USH2A missense variant c.2802T&gt;G/p.C934W (4.9%). Carrier prevalence of these variants was significantly different (<i>p</i> &lt; 0.0001) than in Europe. USH2A was the most commonly affected RP gene in this East Asian cohort, although sub-population analysis revealed distinct genotype prevalence patterns. While the genotypes are similar between East Asia and European cohorts, variants are specific to East Asia. The identification of several prevalent variants in USH2A and EYS provides an opportunity for the development of therapeutics that are relevant for East Asia patients.

正在进行的色素性视网膜炎（retinitis pigmentosa, RP）临床试验均为基因型特异性研究，且绝大多数试验均以欧洲人群队列作为研究对象。由于不同祖先与人群间存在遗传差异，此类疗法在东亚人群中可能无法发挥预期疗效。本研究于1966年至2022年9月期间开展文献检索，旨在筛选针对东亚人群、报道非综合征性色素性视网膜炎基因型与变异体的队列研究。研究采用人群加权患病率法，以确定整个队列中的各类基因型及个体变异体分布情况，并将常见变异体的携带者患病率与欧洲人群的对应数据进行对比。最终纳入12篇文献，共涉及2932例经临床确诊的东亚RP先证者。本研究共在54个基因中检出876个变异体。最常见的基因型包括USH2A、EYS、RPGR、ABCA4、PRPF31、RHO、RP1、RP2、PDE6B及SNRNP200，其中以USH2A最为常见（占比17.1%）。总体而言，携带临床相关变异体的先证者中，60.5%的个体携带上述基因型之一；876个变异体中有543个（占比62.0%）均位于上述基因范围内。最常被报道的变异体为USH2A错义变异c.2802T>G/p.C934W，占比4.9%。上述变异体的携带者患病率与欧洲人群存在显著差异（p<0.0001）。尽管亚群分析显示不同亚群的基因型患病率存在显著差异，但在本次东亚队列中，USH2A仍是受累最常见的RP相关基因。尽管东亚与欧洲队列的基因型整体相似，但变异体类型具有东亚人群特异性。本次研究在USH2A与EYS基因中检出的多个高频变异体，为开发适配东亚患者的靶向治疗药物提供了可行方向。