Miller Charles, Bohnsack Brenda L, Drackley Andy, Ing Alexander, Rahmani Safa, Ralay Ranaivo Hantamalala, Allegretti Valerie, Rossen Jennifer L
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Ophthalmic Genet. 2025 Apr;46(2):160-165. doi: 10.1080/13816810.2024.2446549. Epub 2025 Jan 6.
Due to the recent advent of gene-targeted retinal therapies, the clinical value of high-yield genetic testing for inherited retinal dystrophies (IRDs) has increased considerably. However, diagnostic yield is limited by the reported patient populations in allele frequency databases. This study aimed to determine the effect of race and ethnicity on diagnostic yield in IRDs.
Retrospective review of individuals with suspected IRD based on clinical findings or diagnosis of associated syndrome who underwent genetic testing between 2009 and 2021. Self-reported race and ethnicity, ophthalmic examination findings, ERG results, and genetic testing findings were collected and analyzed.
In 93 individuals (90 families) with suspected IRD, the diagnostic yield was 72% (67 individuals). The rate of diagnostic yield was not significantly associated with family history, associated syndromes, age at testing, ERG results, or ophthalmic exam findings. Further, higher rates of positive diagnostic yield were not associated with more recent genetic testing. There was a trend toward differences in diagnostic yield between races (77% White, 65% Other, 64% Asian, 50% Black) and ratio of pathogenic/likely pathogenic (P/LP) variants to variants of unknown significance (46%:54% White, 36%:64% Other, 31%:69% Asian, 30%:70% Black).
Current genetic testing for IRDs trends toward higher diagnostic yield and identification of P/LP variants in patients identifying as White compared to other races. In order to prevent negative impacts on access to gene-targeted trials and treatments for non-White patients, wider genetic testing in diverse populations is required to create comprehensive catalogs of gene variants associated with IRDs.
由于近期基因靶向视网膜疗法的出现，遗传性视网膜营养不良（IRD）的高产基因检测的临床价值大幅提高。然而，等位基因频率数据库中报告的患者群体限制了诊断率。本研究旨在确定种族和民族对IRD诊断率的影响。
对2009年至2021年间因临床发现或相关综合征诊断而疑似患有IRD并接受基因检测的个体进行回顾性研究。收集并分析自我报告的种族和民族、眼科检查结果、视网膜电图（ERG）结果以及基因检测结果。
在93名（90个家庭）疑似IRD患者中，诊断率为72%（67名个体）。诊断率与家族史、相关综合征、检测时年龄、ERG结果或眼科检查结果无显著关联。此外，较高的阳性诊断率与更近的基因检测无关。不同种族之间的诊断率存在差异趋势（白人77%，其他种族65%，亚洲人64%，黑人50%），以及致病/可能致病（P/LP）变异与意义未明变异的比例（白人46%:54%，其他种族36%:64%，亚洲人31%:69%，黑人30%:70%）。
与其他种族相比，目前针对IRD的基因检测在自我认定为白人的患者中倾向于更高的诊断率和P/LP变异的识别。为防止对非白人患者获得基因靶向试验和治疗产生负面影响，需要在不同人群中进行更广泛的基因检测，以创建与IRD相关的基因变异综合目录。
