A novel mutation in the MIP gene is associated with autosomal dominant congenital nuclear cataract in a Chinese family

PURPOSE: Congenital cataracts are a clinically and genetically heterogeneous lens disorder. The purpose of this study was to identify the genetic mutation and the molecular phenotype responsible for the presence of autosomal dominant congenital nuclear cataract disease in a Chinese family. METHODS: Patients were given physical examinations and their blood samples were collected for DNA extraction. Genotyping was performed by microsatellite markers and logarithm-of-odds (LOD) scores were calculated using the LINKAGE programs. Mutation detection was performed by direct sequencing. RESULTS: Linkage to the major intrinsic protein (MIP) locus was identified. Sequencing MIP revealed an A→G transition at nucleotide position c.530, which caused a conservative substitution of Tyr to Cys at codon 177 (P.Y177C). The Y177C mutation is located in the fifth transmembrane sequence. This mutation was identified in all affected individuals but is not found in any of the 100 control chromosomes. CONCLUSIONS: Our results identify that the c.530 (A→G) mutation in MIP is responsible for the Chinese pedigree. Our results further identify that the mutation in MIP is responsible for congenital cataract. The mutation found in our study broadens the spectrum of MIP mutations.