Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; John P. Hussmann Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
J AAPOS. 2022 Dec;26(6):302.e1-302.e6. doi: 10.1016/j.jaapos.2022.08.529. Epub 2022 Nov 4.
Early-onset glaucoma is a potentially sight-threatening condition with high heritability. Next generation sequencing is a cost-effective alternative to individual gene screening that could expedite its diagnosis. However, the diagnostic yield of multigene panel assays for early-onset glaucoma varies according to the tested population. The purpose of this study was to ascertain the diagnostic yield of next generation sequencing panels in our cohort and to identify population characteristics that increase such yield.
We conducted a retrospective review of the medical records of consecutive patients from November 2016 to August 2021 who were evaluated at our clinics for early-onset glaucoma and had undergone next generation sequencing panels for molecular diagnosis.
A total of 118 patients were included, in 22 of whom (19%) a causative variant was identified. Diagnostic yield varied by age of onset: of 60 patients with onset at <3 years of age, 19 (32%) had such variants identified. In contrast, of 58 patients with later-onset glaucoma, 3 (5%) had said variants identified (P = 0.0003). Other metrics that increased diagnostic yield were presence of additional ocular anomalies (P = 0.0092) and identifying ethnicity as White (compared with non-White, P = 0.0001).
In childhood glaucoma, earlier age of onset is correlated with higher likelihood of pathogenic variant identification. The large proportion of unsolved cases indicates a robust opportunity for gene discovery and genetic therapy targets in early-onset glaucoma patients.
早发性青光眼是一种具有高度遗传性的潜在致盲性疾病。下一代测序是一种比个体基因筛查更具成本效益的替代方法，可以加速其诊断。然而，多基因面板检测在早发性青光眼患者中的诊断效果因所检测的人群而异。本研究旨在确定下一代测序面板在我们的队列中的诊断效果，并确定增加这种效果的人群特征。
我们对 2016 年 11 月至 2021 年 8 月期间在我们的诊所就诊的连续早发性青光眼患者的病历进行了回顾性分析，这些患者接受了下一代测序面板进行分子诊断。
共纳入 118 例患者，其中 22 例（19%）发现了致病变异。诊断效果因发病年龄而异：60 例发病年龄<3 岁的患者中，有 19 例（32%）发现了此类变异。相比之下，58 例发病年龄较大的青光眼患者中，有 3 例（5%）发现了此类变异（P=0.0003）。其他增加诊断效果的指标包括存在其他眼部异常（P=0.0092）和将种族鉴定为白人（与非白人相比，P=0.0001）。
在儿童青光眼患者中，发病年龄越早，致病性变异的可能性越大。未解决的病例比例很大，这表明在早发性青光眼患者中发现基因和遗传治疗靶点具有很大的机会。
