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Variable Anterior Segment Dysgenesis And Cardiac Anomalies Caused By A Novel Truncating Variant Of Foxc1, Mariya R. Ahmed, Saumil Sethna, Laura A. Krueger, Michael B. Yang, Robert B. Hufnagel

Biology Graduate Research

Anterior segment dysgenesis (ASD) encompasses a wide spectrum of developmental abnormalities of the anterior ocular segment, including congenital cataract, iris hypoplasia, aniridia, iridocorneal synechiae, as well as Peters, Axenfeld, and Rieger anomalies. Here, we report a large five-generation Caucasian family exhibiting atypical syndromic ASD segregating with a novel truncating variant of FOXC1. The family history is consistent with highly variable autosomal dominant symptoms including isolated glaucoma, iris hypoplasia, aniridia, cataract, hypothyroidism, and congenital heart anomalies. Whole-exome sequencing revealed a novel variant [c.313_314insA; p.(Tyr105*)] in FOXC1 that disrupts the α-helical region of the DNA-binding forkhead box domain. In vitro studies …