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bioRxiv · 10.1101/042515

Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract

Owen M Siggs·Shari Javadiyan·Shiwani Sharma·Emmanuelle Souzeau·Karen M Lower·Deepa A Taranath·Jo Black·John Pater·John G. Willoughby·Kathryn P Burdon·Jamie E Craig
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Abstract

Congenital cataract is a rare but severe paediatric visual impediment, often caused by variants in one of several crystallin genes that produce the bulk of structural proteins in lens. Here we describe a pedigree with autosomal dominant isolated congenital cataract and linkage to the crystallin gene cluster on chromosome 22. No rare single nucleotide variants or short indels were identified by whole-exome sequencing, yet copy number variant analysis revealed a duplication spanning both CRYBB1 and CRYBA4. While the CRYBA4 duplication was complete, the CRYBB1 duplication was not, with the duplicated CRYBB1 product predicted to create a gain of function allele. This association suggests a new genetic mechanism for the development of isolated congenital cataract.\n\nGrant informationSupported by the National Health and Medical Research Council\n\nConflict of interestthe authors declare no conflict of interest.

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Owen M Siggs, Shari Javadiyan, Shiwani Sharma, Emmanuelle Souzeau, Karen M Lower, Deepa A Taranath, Jo Black, John Pater, John G. Willoughby, Kathryn P Burdon, Jamie E Craig. 2016-03-05. Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract. https://doi.org/10.1101/042515

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