Abstract
Congenital cataract is a rare but severe paediatric visual impediment, often caused by mutations 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 one or both products predicted to create a gain of function allele. This association suggests a new genetic mechanism for the development of isolated congenital cataract.