Diagnostic yield of next generation sequencing gene panel assays for early-onset glaucoma in an ethnically diverse...

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.