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

## TL;DR

A partial duplication in the CRYBB1-CRYBA4 gene region is linked to a hereditary form of congenital cataract in children.

## Contribution

A new genetic mechanism involving partial duplication of CRYBB1 and CRYBA4 is identified for autosomal dominant congenital cataract.

## Key findings

- A duplication spanning CRYBB1 and CRYBA4 was found in a family with autosomal dominant congenital cataract.
- The CRYBB1 duplication is incomplete and may result in a gain of function allele.
- No rare single nucleotide variants or short indels were found in the affected family.

## 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.

Supported by the National Health and Medical Research Council

the authors declare no conflict of interest.