De Geer Karl, Löfgren Stefan, Lindstrand Anna, Kvarnung Malin, Björck Erik
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden.
Acta Ophthalmol. 2025 May;103(3):327-338. doi: 10.1111/aos.16804. Epub 2024 Dec 6.
This study aimed to characterize clinical and genetic findings in a Swedish cohort with inherited retinal disease (IRD), identify predictors for achieving a molecular diagnosis and evaluate the effects of increased genetic testing over time.
Clinical and genetic data from 324 nonrelated IRD index individuals referred for genetic testing in the Stockholm region between 2016 and 2023 were collected retrospectively and analysed by clinical subtype, age of onset and testing period (2016-2020 vs. 2021-2023). Logistic regression was used to calculate odds ratios for age of onset and family history on the likelihood of achieving a molecular diagnosis.
The diagnostic yield was 55% and involved 56 genes. In 10% of solved individuals, the molecular diagnosis refined the clinical diagnosis. For each 1-year increase in age of onset, the odds of achieving a molecular diagnosis decreased by 3% (odds ratio 0.97, 95% confidence interval 0.96-0.98). A positive family history doubled the odds (odds ratio 2.1, 95% confidence interval 1.3-3.4). The use of genetic testing increased 2.1-fold and the number of molecular diagnoses increased 1.6-fold relative to the population of the Stockholm region between the two testing periods.
This study adds to the knowledge of the clinical and genetic landscape of IRDs in Sweden and establishes age of onset and family history as significant predictors for achieving a molecular diagnosis. Increased genetic testing on a population level substantially increased the number of individuals receiving a molecular diagnosis with a high diagnostic yield compared to other rare diseases.
本研究旨在描述瑞典遗传性视网膜疾病（IRD）队列的临床和基因学发现，确定实现分子诊断的预测因素，并评估随着时间推移增加基因检测的效果。
回顾性收集了2016年至2023年期间在斯德哥尔摩地区转诊进行基因检测的324名非亲属IRD索引患者的临床和基因数据，并按临床亚型、发病年龄和检测时期（2016 - 2020年与2021 - 2023年）进行分析。采用逻辑回归计算发病年龄和家族史对实现分子诊断可能性的优势比。
诊断率为55%，涉及56个基因。在10%的确诊患者中，分子诊断细化了临床诊断。发病年龄每增加1岁，实现分子诊断的几率降低3%（优势比0.97，95%置信区间0.96 - 0.98）。阳性家族史使几率增加一倍（优势比2.1，95%置信区间1.3 - 3.4）。与两个检测时期之间斯德哥尔摩地区的人群相比，基因检测的使用增加了2.1倍，分子诊断的数量增加了1.6倍。
本研究增加了对瑞典IRD临床和基因情况的了解，并确定发病年龄和家族史是实现分子诊断的重要预测因素。与其他罕见疾病相比，在人群层面增加基因检测显著增加了接受分子诊断的个体数量，且诊断率较高。
