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Phenotype–genotype correlations and emerging pathways in ocular anterior segment dysgenesis


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, as well as syndromal associations. These conditions have a significant impact on vision due to disruption of the visual axis, and also secondary glaucoma which occurs in over 50% of patients. Ocular anterior segment disorders occur due to a complex interplay of developmental, embryological and genetic factors, and often have phenotypic overlaps and genetic heterogeneity. Here we present a review of the clinical features and genes associated with aniridia, Axenfeld and Rieger anomalies, primary congenital glaucoma, Peters anomaly, and syndromic forms of these conditions. We also highlight phenotype–genotype correlations, recent discoveries with next-generation sequencing which broaden known phenotypes, and new anterior segment genes and pathways. We provide a guide towards genetic diagnosis for clinicians investigating patients with anterior segment dysgenesis.

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RVJ and JRG acknowledge support from NHMRC grant APP1116360, the NSW Office of Health and Medical Research, Costco, the Sydney Research Excellence Initiative and the Ophthalmic Research Institute of Australia.

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Ma, A.S., Grigg, J.R. & Jamieson, R.V. Phenotype–genotype correlations and emerging pathways in ocular anterior segment dysgenesis. Hum Genet 138, 899–915 (2019).

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