Alpha-b crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans

Congenital cataracts are an important cause of bilateral visual impairment in infants. In a four-generation family of English descent, we mapped domin ant congenital posterior polar cataract to chromosome 11q22-q22.3. The maxi mum LOD score, 3.92 at recombination fraction 0, was obtained for marker D1 1S898, near the gene that encodes crystallin alpha-B protein (CRYAB). By se quencing the coding regions of CRYAB, we found in exon 3 a deletion mutatio n, 450delA, that is associated with cataract in this family. The mutation r esulted in a frameshift in codon 150 and produced an aberrant protein consi sting of 184 residues. This is the first report of a mutation, in this gene , resulting in isolated congenital cataract.