Genomics and molecular mechanisms in glaucoma and anterior segment abnormalities

Abstract

AbstractOcular anterior segment disorders have a significant impact on vision and may lead to glaucoma in over 50% of cases. They occur due to a complex interplay of developmental and genetic factors, and there are often marked phenotypic overlaps and genetic heterogeneity. Disorders of the anterior segment of the eye encompass a variety of clinical presentations including aniridia, Axenfeld and Rieger anomalies, primary congenital glaucoma, Peters anomaly, and there are a number of syndromal associations. Several genotype‐phenotype correlations are present, and genomic approaches have facilitated broadening of known phenotypes and led to identification of new anterior segment disease genes and pathways. Key disease genes include FOXC1, PITX2, CYP1B1, FOXE3, and PAX6, and there are a number of newly identified and less frequently reported disease genes including GJA8, CPAMD8, PXDN and COL4A1. Whole exome and whole genome sequencing approaches facilitate genetic diagnosis in these genetically heterogeneous disorders. These approaches, in combination with cellular and animal model studies, assist in elucidation of novel disease genes and molecular mechanisms contributing to glaucoma and anterior segment abnormalities.