Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract
Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract
Date
2017-03-08
Authors
Siggs, Owen M
Javadiyan, Shahrbanou
Sharma, Shiwani
Souzeau, Emmanuelle
Lower, Karen Marie
Taranath, Deepa A
Black, J A
Pater, John Brian
Willoughby, John G
Burdon, Kathryn Penelope
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
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 the 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 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.
Description
This author accepted manuscript is made available following 6 month embargo from date of publication (March 2017) in accordance with the publisher’s copyright policy
Keywords
Cataract,
Congenital cataract,
paediatric visual impediment,
crystallin genes,
chromosome 22,
CRYBB1,
CRYBA4,
CRYBA4,
genetics
Citation
Owen M Siggs, Shari Javadiyan, Shiwani Sharma, Emmanuelle Souzeau, Karen M Lower, Deepa A Taranath, . . . Jamie E Craig. (2017). Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract. European Journal of Human Genetics, European Journal of Human Genetics, 2017.