title: Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3).
abstract: We describe a four-generation family with fully penetrant, autosomal dominant, congenital cataracts (ADCC), presenting with morphologically homogeneous "zonular pulverulent" cataracts (CZP) and typical early-onset phenotype. Linkage analysis was performed with a panel of polymorphic markers mapped to all genomic regions of ADCC susceptibility. Contiguous significant two-point lod scores were generated at autosomal region 13q11-q13 and further linkage and haplotype studies confined the disease locus to 13q11, supporting a previous linkage of CZP (specifically CZP3) to 13q11. Mutations in a gap-junction protein, connexin 46 (alphaa3 subunit or GJA3), have recently been reported as being linked to the 13q11 region. Mutational analysis of connexin 46 in our family revealed a C-->T at position 560 (P187L) of the cDNA sequence creating a novel MnlI restriction site that segregated with affected members of the pedigree. This family represents a second report of CZP3 linkage to 13q and is associated with a novel mutation in the connexin 46 (GJA3) gene.
authors.affiliation: Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK. m.rees@auckland.ac.nz
authors.forename: M I
authors.initials: MI
authors.lastname: Rees
authors.forename: P
authors.initials: P
authors.lastname: Watts
authors.forename: I
authors.initials: I
authors.lastname: Fenton
authors.forename: A
authors.initials: A
authors.lastname: Clarke
authors.forename: R G
authors.initials: RG
authors.lastname: Snell
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: J
authors.initials: J
authors.lastname: Gray
mesh_terms: D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13; D017630:Connexins / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D017630:Connexins; D017931:DNA Primers; C082917:GJA3 protein, human