Commercial Gene Panels for Congenital Anterior Segment Anomalies: Are They All the Same?

Maria Fernanda Villalba; Chris Michael Li; Parastou Pakravan; Guney Bademci; Ta Chen Peter Chang

doi:10.1016/j.ajo.2023.02.025

Commercial Gene Panels for Congenital Anterior Segment Anomalies: Are They All the Same?

Am J Ophthalmol. 2023 Jul:251:90-103. doi: 10.1016/j.ajo.2023.02.025. Epub 2023 Mar 10.

Authors

Maria Fernanda Villalba¹, Chris Michael Li², Parastou Pakravan², Guney Bademci³, Ta Chen Peter Chang⁴

Affiliations

¹ From the Bascom Palmer Eye Institute (M.F.V., T.C.P.C.), University of Miami Miller School of Medicine, Miami, Florida, USA; John P. Hussmann Institute for Human Genomics (M.F.V., G.B.), University of Miami Miller School of Medicine, Miami, Florida, USA; University of Miami Miller School of Medicine (M.F.V., C.M.L., P.P.), Miami, Florida, USA.
² University of Miami Miller School of Medicine (M.F.V., C.M.L., P.P.), Miami, Florida, USA.
³ John P. Hussmann Institute for Human Genomics (M.F.V., G.B.), University of Miami Miller School of Medicine, Miami, Florida, USA; Department of Human Genetics (G.B.), University of Miami Miller School of Medicine, Miami, Florida, USA.
⁴ From the Bascom Palmer Eye Institute (M.F.V., T.C.P.C.), University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address: t.chang@med.miami.edu.

PMID: 36906093
PMCID: PMC10247492 (available on 2024-07-01)
DOI: 10.1016/j.ajo.2023.02.025

Abstract

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

Design: Comparison of commercial genetic testing panels.

Methods: This observational study gathered publicly available information on NGS-MGP from 5 commercial laboratories for the following: 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 1 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. The consensus rate varied between 16% and 50%, and the dissensus rate varied between 14% and 74%. After pooling concurrent genes from all conditions, 20% of these genes were concurrent in 2 or more conditions. For both cataract and glaucoma, concurrent genes had significantly stronger correlation with the condition than standalone genes.

Conclusions: The genetic testing of CASAs using NGS-MGPs is complicated, owing to their number, variety, and phenotypic and genetic overlap. Although 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 in making decisions of panel selection for the diagnosis of CASAs.

Publication types

Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cataract*
Coloboma*
Corneal Dystrophies, Hereditary*
Glaucoma* / genetics
Humans
Microphthalmos*
Prospective Studies

Supplementary concepts

Anterior segment mesenchymal dysgenesis
Axenfeld-Rieger syndrome

Grants and funding

P30 EY014801/EY/NEI NIH HHS/United States