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Abstract #66311 Published in IGR 17-3
Sporadic and Familial Congenital Cataracts: Mutational Spectrum and new Diagnoses using Next-Generation Sequencing
Ma AS; Grigg JR; Ho G; Prokudin I; Farnsworth E; Holman K; Cheng A; Billson FA; Martin F; Fraser C; Mowat D; Smith J; Christodoulou J; Flaherty M; Bennetts B; Jamieson RVHuman Mutation 2016; 37: 371-384
Congenital cataracts are a significant cause of lifelong visual loss. They may be isolated or associated with microcornea, microphthalmia, anterior segment dysgenesis (ASD) and glaucoma, and there can be syndromic associations. Genetic diagnosis is challenging due to marked genetic heterogeneity. In this study, next-generation sequencing (NGS) of 32 cataract-associated genes was undertaken in 46 apparently non-syndromic congenital cataract probands, around half sporadic and half familial cases. We identified pathogenic variants in 70% of cases, and over 68% of these were novel. In almost two-thirds (20/33) of these cases, this resulted in new information about the diagnosis and/or inheritance pattern. This included identification of: new syndromic diagnoses due to NHS or BCOR mutations; complex ocular phenotypes due to PAX6 mutations; de novo autosomal dominant or X-linked mutations in sporadic cases; and mutations in two separate cataract genes in one family. Variants were found in the crystallin and gap junction genes, including the first report of severe microphthalmia and sclerocornea associated with a novel GJA8 mutation. Mutations were also found in rarely reported genes including MAF, VIM, MIP, and BFSP1. Targeted NGS in presumed non-syndromic congenital cataract patients provided significant diagnostic information in both familial and sporadic cases. This article is protected by copyright. All rights reserved.
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Classification:
9.1.1 Congenital glaucoma, Buphthalmos (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
9.1.2 Juvenile glaucoma (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)