title: Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract.
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.
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Siggs
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Shari
authors.initials: S
authors.lastname: Javadiyan
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Shiwani
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Souzeau
authors.affiliation: Department of Haematology and Genetic Pathology, Flinders University, Bedford Park, South Australia, Australia.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Lower
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Deepa A
authors.initials: DA
authors.lastname: Taranath
authors.affiliation: Department of Ophthalmology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
authors.forename: Jo
authors.initials: J
authors.lastname: Black
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.|Department of Ophthalmology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Pater
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: John G
authors.initials: JG
authors.lastname: Willoughby
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D056915:DNA Copy Number Variations; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D038205:beta-Crystallin A Chain / Q000235:genetics*; D038206:beta-Crystallin B Chain / Q000235:genetics*
chemical_list: C103907:CRYBA4 protein, human; C105601:CRYBB1 protein, human; D038205:beta-Crystallin A Chain; D038206:beta-Crystallin B Chain