title: A nonsense mutation in CRYBB1 associated with autosomal dominant cataract linked to human chromosome 22q.
abstract: Autosomal dominant cataract is a clinically and genetically heterogeneous lens disorder that usually presents as a sight-threatening trait in childhood. Here we have mapped dominant pulverulent cataract to the beta-crystallin gene cluster on chromosome 22q11.2. Suggestive evidence of linkage was detected at markers D22S1167 (LOD score [Z] 2.09 at recombination fraction [theta] 0) and D22S1154 (Z=1.39 at theta=0), which closely flank the genes for betaB1-crystallin (CRYBB1) and betaA4-crystallin (CRYBA4). Sequencing failed to detect any nucleotide changes in CRYBA4; however, a G-->T transversion in exon 6 of CRYBB1 was found to cosegregate with cataract in the family. This single-nucleotide change was predicted to introduce a translation stop codon at glycine 220 (G220X). Expression of recombinant human betaB1-crystallin in bacteria showed that the truncated G220X mutant was significantly less soluble than wild type. This study has identified the first CRYBB1 mutation associated with autosomal dominant cataract in humans.
mesh_terms: D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D018389:Codon, Nonsense; D003459:Crystallins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016415:Sequence Alignment; D038206:beta-Crystallin B Chain
chemical_list: C105601:CRYBB1 protein, human; D018389:Codon, Nonsense; D003459:Crystallins; D038206:beta-Crystallin B Chain