板层状鱼鳞病患者转谷氨酰胺酶1活性缺失及其基因突变  

A Nonsense Mutation in Transglutaminase1Gene and Loss of Enzyme Activity in a Family with Lamellar Ichthyosis

作　　者：杨勇[1] 马铁牛[2] 杨海珍[1] 卜定方[1] 汪科[1] 涂平[1] 朱学骏[1] 

机构地区：[1]北京大学第一医院皮肤科,100034 [2]天津长征医院皮肤科

出　　处：《中华皮肤科杂志》2003年第9期487-489,共3页Chinese Journal of Dermatology

基　　金：北京大学医学部"创建世界一流大学行动计划"青年启动基金

摘　　要：目的检测一板层状鱼鳞病家系中患者转谷氨酰胺酶1的活性及其编码基因的突变。方法以免疫组化法检测患者转谷氨酰胺酶1的活性,PCR扩增该基因的全部编码序列,并行DNA测序。结果患者皮肤转谷氨酰胺酶1的活性完全缺失。PCR结合DNA测序发现患者该基因第4外显子存在异常:第604位碱基由胞嘧啶突变为胸腺嘧啶,使第202位氨基酸由谷氨酰胺(Q)变为终止密码(R202X),导致其编码的蛋白缺失了C端的615个氨基酸。其父母皆为杂合子。结论板层状鱼鳞病患者转谷氨酰胺酶1的活性完全缺失,是其转谷氨酰胺酶1基因的无义突变,引起编码的蛋白缺陷。Objective To detect the activity of transglutaminase1(TGM1)and gene mutation in a family with lamellar ichthyosis.Methods Immunohistochemistry technique was used to detect the activity of transglutaminase1.Complete encoding sequences of TGM1gene were analyzed in this family by using PCR-DNA sequencing.Results No activity of transglutaminase1was detected in the proband's skin.A nonsense mutation of C604T located in exon4of TGM1gene was identified by PCR-DNA sequencing,which caused a premature termination of Q202X and a defective polypeptide truncated by615amino acids in C-terminus.A heterozygous C604T mutation was carried by both of the proband' s parents.Conclusions The proband of lamellar ichthyosis in this family shows loss of transglutaminase1activity,which is resulted from a truncated transglutaminase1coded by the homozygous mutant TGM1gene.

关 键 词：板层状鱼鳞病 转谷氨酰胺酶1 活性 编码基因 DNA测序 基因突变 蛋白缺陷 

分 类 号：R758.52[医药卫生—皮肤病学与性病学]