晶状体膜蛋白MIP基因C末端一个新的错义突变导致双眼多形性先天性白内障  

A novel missense mutation in MIP gene resulted in polymorphic cataract

作　　者：林辉[1] 王丽[1] 周南[1] 苏虹[1] 谷静芝[1] 齐艳华[1] 

机构地区：[1]哈尔滨医科大学附属二院眼科,150086

出　　处：《中华医学遗传学杂志》2008年第1期6-10,共5页Chinese Journal of Medical Genetics

基　　金：黑龙江省卫生厅课题（2003-071,2006-147）;黑龙江省教育厅科技项目（10531119）;黑龙江省教育厅研究生创新科研项目

摘　　要：目的定位一个双眼多形性先天性白内障家系的致病位点，寻找疾病家系的致病基因。方法应用ABI-MD10试剂盒中的常染色体382个微卫星位点，对一个常染色体显性、双眼具有不同白内障形态的先天性白内障家系进行全基因组扫描。MLINK软件进行两点连锁分析。直接测序候选基因外显子。结果在D12S83处获得最大LOD值Zmax=5．44（θ=0），该家系致病位点被定位到12p11．2-q15之间的区域上，在该区域的白内障候选基因晶状体膜蛋白基因（majorintrinsicprotein，M驴）的第4外显子中发现单个碱基错义突变，702ntG→A，导致P．R233K。结论该先天性白内障由MIP基因702ntG→A突变所致，导致MIP蛋白质的C-末端中p-R233K，从而可能减少了氢键的形成，影响了该蛋白C-末端的稳定性，推测影响了MIP对水的调节及由该蛋白质形成的细胞之间的连接。这一新突变为目前世界上首次报道。Objective To map the disease locus for a congenital cataract family, and detect the disease-causing gene. Melhods An autosomal dominant congenital cataract family was genotyped by genome wide scan using 382 autosomal microsatellite markers from ABI-MD10. Two-point linkage analysis was carried out by the MLINK program. Results The disease locus of this family was mapped at 12p11.2-q15. Sequence analysis of a candidate gene-major intrinsic protein （MIP） revealed a novel missense mutation G→A at the nucleotide 702 in exon 4, which resulted in a substitution of arginine to lysine at codon 233 （p. R233K）. Conclusion The mutation G→A at nt702 in MIP gene was associated with the binocular polymorphic congenital cataract in the family. This transition occurring at the C-terminus of MIP might decrease the stability of the C-end of the protein and impact the function of the protein.

关 键 词：晶状体膜蛋白基因 错义突变 双眼多形性先天性白内障 

分 类 号：R776.1[医药卫生—眼科] R378[医药卫生—临床医学]