Genetic Variants Associated with Anterior Segment Dysgenesis in South Florida

Abstract

Background Anterior segment dysgenesis (ASD) comprises a wide spectrum of developmental conditions affecting the cornea, iris, and lens, which may be associated with abnormalities of other organs. Mutations in over 20 genes have been shown to cause ASD. To identify disease-causing variants, we performed exome sequencing in 24 South Florida families with ASD. Results We identified 12 likely causative variants in 10 families (42%), including single nucleotide or small insertion-deletion variants in B3GLCT, BMP4, CYP1B1, FOXC1, FOXE3, GJA1, PXDN, and TP63, and a large copy number variant involving PAX6 . Four variants were novel. Each variant was detected only in one family. Conclusions Presence of rare variants in multiple genes leading to ASD explains its genetic basis in over 40% of patients from South Florida. Exome sequencing for ASD allows us to identify causative variants, thus improving our ability to explain the underlying etiology in more families and to assist them with genetic counseling.