A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance.

C ongenital or paediatric cataract is a phenotypically and genetically heterogeneous disorder consisting of lens opacities in early life. Thirteen genes have been described for autosomal dominant congenital cataract (ADCC). These include genes for seven members of the crystallin family, 2 which are responsible for the refractive index and transparency of the lens, two connexin genes 4 and major intrinsic protein of the lens (MIP) which are involved in the transport directly between cells of small metabolites and water, respectively, the cytoskeletal protein beaded filament structural protein-2 (BFSP2), and transcription factors paired-like homeodomain transcription factor-3 (PITX3) and heat shock factor-4 (HSF4). Five additional loci have been described on chromosomes 1pter-p36.1, 15q21q22, 17p13, 17q24, and 20p12-q12. We used a linkage approach to investigate these 13 genes and five loci in a large pedigree from Victoria, Australia, with zonular pulverulent cataract with the aim of identifying the causative mutation.