Commercial Gene Panels for Congenital Anterior Segment Anomalies: are they all the same?

PURPOSE: We compared next-generation sequencing multigene panels (NGS-MGP) from 5 commercial laboratories to inform the ophthalmologist's decision-making in diagnostic genetic testing for congenital anterior segment anomalies (CASA).

DESIGN: Comparison of commercial genetic testing panels.

METHODS: This observational study gathered publicly available information on NGS-MGP from 5 commercial laboratories for: cataracts, glaucoma, anterior segment dysgenesis (ASD), microphthalmia-anophthalmia-coloboma (MAC), corneal dystrophies, and Axenfeld-Rieger syndrome (ARS). We compared gene panel composition, consensus rate (genes covered by all the panels per condition, "concurrent"), dissensus rate (genes covered by only one panel per condition, "standalone"), and intronic variant coverage. For individual genes, we compared publication history and association with systemic conditions.

RESULTS: Altogether, cataract, glaucoma, corneal dystrophies, MAC, ASD, and ARS panels tested 239, 60, 36, 292, and 10 discrete genes, respectively. Consensus rate varied between 16% and 50%, and dissensus rate varied between 14% and 74%. After pooling concurrent genes from all conditions, 20% of these genes were concurrent in two or more conditions. For both cataract and glaucoma, concurrent genes had significantly stronger correlation to the condition than standalone genes.

CONCLUSIONS: The genetic testing of CASA using NGS-MGPs is complicated, owing to their number, variety, and phenotypic and genetic overlap. While the inclusion of additional genes, such as the standalone ones, might increase diagnostic yield, these genes are also less well-studied, indicating uncertainty over their role in CASA pathogenesis. Rigorous prospective diagnostic yield studies of NGS-MGPs will aid decisions of panel selection for the diagnosis of CASA.