A substitution of arginine to lysine at the COOH-terminus of MIPcaused a different binocular phenotype in a congenital cataract family

[摘要] Purpose: To detect the cataractogenetic mutation for asix-generation family of Chinese origin with autosomal dominantbinocular polymorphic cataracts.Methods: A genome wide scan was performed using 382fluorescent-labeled microsatellite markers. Multiple polymerase chainreaction (PCR) was performed according to the protocols previouslydescribed. Two-point linkage analysis was performed with the FASTLINKversion of the MLINK in Linkage Program Package. The candidate gene wasscreened by direct sequencing.Results: The disease locus was mapped to a 61 cM region onchromosome 12 defined by D12S310 and D12S351 near the major intrinsicprotein gene (MIP). The maximum two-point lod score of 5.44 wasobtained at marker D12S83 at θ=0.00. Direct sequencing of theencoding region of the candidate gene revealed a novel missense mutationG>A in exon 4 at nucleotide 702, which caused the replacement ofarginine to lysine at codon 233 (p.R233K).Conclusions: The change located in the α-helix domain of theCOOH-terminus of MIP was determined to be associated with the binocularpolymorphic cataract in this study. It suggests that arginine in thisdomain plays a crucial role in the function of the carboxyl-end of thisprotein and provides a helpful clue to further studies on completelyunderstanding the physiological significance of MIP and its role inthe formation of cataract.

[学科分类] 生物化学/生物物理