Gene Conversion Mutation in Crystallin, β-B2 (CRYBB2) in a Chilean Family with Autosomal Dominant Cataract
Presented as a poster at: Association for Research in Vision and Ophthalmology meeting, May 2005, Ft. Lauderdale, Florida.
Received 6 October 2005; accepted 22 September 2006. published online 17 January 2007.
Purpose
To map and identify the mutated gene for autosomal dominant cataract (ADC) in a large Chilean family (ADC53).
Design
Experimental study.
Participants
Large Chilean family with ADCs.
Methods
Linkage analyses using genome-wide polymorphic DNA markers were performed on a family with variable expression of cataracts to map the mutated gene to a chromosome; 2-point lod scores were calculated. Candidate genes in the region of the maximum lod score were sequenced. We compared haplotypes (alleles at closely linked markers) in families with previously reported mutations of the crystallin, β-B2 gene (CRYBB2).
Main Outcome Measures
Identification of the causative mutation in the ADC53 family.
Results
The ADC locus mapped to chromosome 22 in the region of a cluster of lens β crystallin genes (CRYBB3, CRYBB2, CRYBB1, and CRYBA4 and the pseudogene CRYBB2P1). We sequenced CRYBB1 and CRYBB2 and found a previously reported mutation and a variant in exon 6 of CRYBB2 that cosegregate with the disease; these changes in CRYBB2 are in the reference (normal) sequence of an adjacent gene CRYBB2P1, a pseudogene. The haplotypes in the ADC53 Chilean family were different from the 2 previously reported families with the mutation.
Conclusions
The cataracts in the ADC53 Chilean family are caused by a mutation in the CRYBB2 gene; as the 2 variations in CRYBB2 are identical to the reference sequence of pseudogene CRYBB2P1, which has over 97% homology to CRYBB2, a gene conversion probably has occurred. Based on haplotype analyses, the mutation and variant are likely to be caused by independent gene conversions in our family and the previously reported families.
1Department of Ophthalmology, Rocky Mountain Lions Eye Institute, Denver, Colorado.
3University of Colorado School of Medicine, Denver, Colorado.
4Departamento de Oftalmologia, Universidad de Concepción, Servicio de Oftalmologia, Hospital Clínico Regional de Concepción “Guillermo Grant Benavente,” Concepción, Chile.
5Department of Pediatrics, University of California, Irvine, California.
Correspondence and reprint requests to J. Bronwyn Bateman, MD, Department of Ophthalmology, University of Colorado, 1675 North Ursula Street, Box F-731, Aurora, CO 80045.
Manuscript no. 2005-966.
Supported by the National Eye Institute, Bethesda, Maryland (grant no. EY08282 [JBB]).
ABSTRACT