Clinical and Genetic Studies of an Autosomal Dominant Form of Congenital Cataract

Abstract

Abstract: : Purpose: To report the clinical phenotype and the genotypic features of a five generation Mormon family affected by autosomal dominant congenital nuclear cataract (adNCat) Methods: Ophthalmic examination and genetic study were conducted in one large kindred with an autosomal dominant form of congenital cataract. Genomic DNA was extracted from the blood samples of family members. Genotyping analysis was performed using polymorphic DNA markers encompassing Paired-like Homeodomian Transcription (PITX3) gene (D10S1239, D10S1240, and D10S1697) and a locus for congenital nuclear sclerosis on 2p (D2S1262, D2S2333, D2S1790). Each of the 4 exons of PITX3 gene was amplified by PCR and sequenced. Results: One large Mormon family with autosomal dominant congenital cataract underwent ophthalmological examination and genetic study. Of the 44 individuals who were at risk of inheriting the disease, 24 were affected. Based on family history and clinical diagnosis, the type of cataract was determined to be nuclear sclerosis. The disease phenotype progressed from nuclear sclerosis to total cataract. The onset of disease phenotype is at birth. Linkage analysis with short tandem repeat polymorphic markers revealed no positive linkage to 10q24-25 or 2p locus. Sequence analysis did not idnetify any mutation in the coding exons and splice junctions of PITX3. Conclusions: We report autosomal dominant congenital cataract in the form of nuclear sclerosis in one large Mormon family. Genetic analysis excluded known loci for congenital nuclear sclerosis. A whole genome scan to map the disease gene is in progress. Identification and characterization of a gene for congenital cataract will enhance our understanding of the underlying pathogenetic mechanisms in lens physiology and pathology.

Keywords: cataract • candidate gene analysis • gene mapping