ABSTRACT
Congenital cataracts are a common major abnormality of the eye that frequently cause blindness in infants. At least a third of all cases are familial; autosomal dominant congenital cataract (ADCC) appears to be the most common familial form in the Western world. We have mapped an ADCC gene in family ADCC-2 to chromosome 21q22.3 near the alpha-crystallin gene CRYAA. By sequencing the coding regions of CRYAA, we found that a missense mutation, R116C, is associated with ADCC in this family.
Subject(s)
Cataract/genetics , Chromosomes, Human, Pair 21 , Crystallins/genetics , Genes, Dominant , Point Mutation , Amino Acid Sequence , Animals , Cataract/congenital , Chromosome Mapping , Exons , Female , Genetic Linkage , Genetic Markers , Humans , Introns , Lod Score , Male , Microsatellite Repeats , Molecular Sequence Data , Pedigree , Sequence Alignment , Sequence Homology, Amino AcidABSTRACT
Congenital cataracts are a common major abnormality of the eye that frequently cause blindness in infants. At least a third of all cases are familial; autosomal dominant congenital cataract (ADCC) appears to be the most common familial form in the Western world. Cerulean cataracts have peripheral bluish and white opacifications in concentric layers with occasional central lesions arranged radially. Although the opacities may be observed during fetal development and childhood, usually visual acuity is only mildly reduced until adulthood, when lens extraction is generally necessary. We have been studying a family (ADCC-1) with cerulean blue ADCC, in which the affected daughter of a first cousin mating was presumed to be homozygous for the cataract gene. Recently, we mapped an ADCC gene in this family to a region of chromosome 22 containing three beta-crystallin genes. Here we report that a chain-termination mutation in CRYBB2 is associated with ADCC in this family.