Sporadic and familial congenital cataracts: mutational spectrum and new diagnoses using next-generation sequencing

Alan S. Ma, John R. Grigg, Gladys Ho, Ivan Prokudin, Elizabeth Farnsworth, Katherine Holman, Anson Cheng, Frank A. Billson, Frank Martin, Clare Fraser, David Mowat, James Smith, John Christodoulou, Maree Flaherty, Bruce Bennetts, Robyn V. Jamieson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

101 Citations (Scopus)
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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 nonsyndromic 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 nonsyndromic congenital cataract patients provided significant diagnostic information in both familial and sporadic cases.

Original languageEnglish
Pages (from-to)371-384
Number of pages14
JournalHuman Mutation
Issue number4
Publication statusPublished - 1 Apr 2016
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Congenital cataract
  • Eye
  • Microcornea
  • Microphthalmia
  • Next-generation sequencing


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