Gene conversion mutation in crystallin, beta-B2 (CRYBB2) in a Chilean family with autosomal dominant cataract.
OBJECTIVE
To map and identify the mutated gene for autosomal dominant cataract (ADC) in a large Chilean family (ADC53).


METHODS
Experimental study.


METHODS
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, beta-B2 gene (CRYBB2).


METHODS
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 beta 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.
Bateman
J Bronwyn
JB
Department of Ophthalmology, Rocky Mountain Lions Eye Institute, Denver, Colorado, USA. bronwyn.bateman@uchsc.edu
von-Bischhoffshaunsen
Fernando R Barria
FR
Richter
Leslie
L
Flodman
Pamela
P
Burch
Douglas
D
Spence
M Anne
MA
D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002677:Chile; D005091:Exons; D005260:Female; D005785:Gene Conversion; D005799:Genes, Dominant; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D038206:beta-Crystallin B Chain / Q000235:genetics*
D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2