Pro 275 Ser纯合突变导致的Ⅱ型遗传性蛋白C缺陷症  

Pro 275 Ser Homozygous Mutation of PROC Gene Causes Type Ⅱ Inherited Protein C Deficiency

作　　者：王剑[1] 戴菁[2] 傅启华[1] 王学锋[2] 王鸿利[3] 

机构地区：[1]上海交通大学医学院附属上海儿童医学中心实验诊断中心 [2]上海交通大学医学院附属瑞金医院临床输血科 [3]上海血液学研究所

出　　处：《血栓与止血学》2009年第4期149-153,共5页Chinese Journal of Thrombosis and Hemostasis

摘　　要：目的对1例Ⅱ型遗传性蛋白C(PC)缺陷症家系进行基因突变的检测。方法分别用发色底物法和ELISA测定血浆蛋白C活性和抗原。用PCR法对先证者PROC基因的9个外显子及其侧翼序列进行扩增,PCR产物经割胶纯化后直接测序,检测其基因突变。家系成员DNA在先证者PROC基因突变区域扩增后测序。突变位点经限制性内切酶分析证实,并经105例健康体检者作对照以排除基因多态性。结果先证者的蛋白C活性和抗原分别为5%和13.9%。PROC基因测序分析发现先证者表现为外显子9区C12625T纯合错义突变,该突变引起编码的蛋白C Pro 275Ser氨基酸替换。结论Pro 275 Ser纯合突变是导致该例先证者Ⅱ型遗传性PC缺陷症的分子机制,该突变为国际首报。Objective To identify the gene mutation of a pedigree with type Ⅱ inherited protein C deficiency. Methods The plasma levels of protein C activity （PC： A） and protein C antigen （PC： Ag） were measured using chromogenic assay and ELISA, respectively. All 9 exons and exon- intron boundaries sequences of PROC genes were amplified by PCR from the proband＇s genomic DNA, the amplified products were purified by gel extraction method and analyzed by direct sequencing. Corresponding PCR fragments from the family members were also sequenced directly. Restriction enzyme analysis was used to confirm the mutation. 100 and 5 healthy donors were used as controls to eliminate the polymorphism. Results.The plasma protein C activity and antigen of the proband were 5% and 13.9%, respectively. Gene analysis revealed that the proband had a homozygous C12625T missense mutation in exon 9 of PROC gene, which would cause the substitution of Pro to Ser at the 275 amino acid. Conclusion The novel C12625T homozygous mutation in exon 9 of protein C gene leads to type Ⅱ inherited protein C deficiency.

关 键 词：蛋白C 缺陷 基因突变 

分 类 号：Q754[生物学—分子生物学]