A novel mutation in major intrinsic protein of the lens gene (MIP) underlies autosomal dominant cataract in a Chinese family.

PURPOSE: To identify the causitive mutation in a five-generation family with autosomal dominant congenital total cataract.
METHODS: Clinical and ophthalmological examinations were performed on the affected and unaffected family members. All the members were genotyped with microsatellite markers at loci that were considered to be associated with cataracts. Linkage analysis was performed after genotyping. A mutation was detected by direct sequencing using gene specific primers.
RESULTS: Affected individuals in this family showed total cataract. The disease gene was mapping between to a 15.5 Mb interval bounded by D12S368 and D12S1676. A positive two-point LOD score (3.21 at recombination fraction 0) was obtained for the marker D12S90, flanked by D12S368 and D12S1052, on chromosome 12q13.1-21.1. This chromosome encompasses the Major Intrinsic Protein (MIP, MIP26) of the lens, also called aquaporin 0 (AQP0). Sequencing the coding regions of MIP revealed a C>T transition at nucleotide 97 in exon 1 that caused a substitution of arginine (R) to cysteine (C) at codon 33 (p.R33C). This mutation cosegregated with all affected individuals and was not observed in unaffected or in 100 normal unrelated individuals.
CONCLUSIONS: This study has identified the first dominant cataract mutation in MIP that is located outside the phylogenetically conserved transmembrane domain.