蛋白C缺陷症四例报告及基因分析  

Gene diagnosis of four patients with protein C deficiency

作　　者：高波[1] 周荣富[1] 欧阳建[1] 陈兵[1] 徐勇[1] 李萍[1] 

机构地区：[1]南京大学医学院附属南京鼓楼医院血液科,210008

出　　处：《中华血液学杂志》2016年第11期966-970,共5页Chinese Journal of Hematology

基　　金：江苏省卫生厅135开放课题（K0605）;江苏省科技厅临床医学科技专项（BL20122005）

摘　　要：目的探讨蛋白C缺陷症的分子发病机制。方法对4例蛋白C缺陷症患者进行常规诊断和基因分析。结果①例1，女，40岁。临床诊断：左下肢深静脉血栓形成。蛋白C活性（PC：C）48％，蛋白S活性（PS：C）26．3％，抗凝血酶活性（AT：C）75．6％。基因检测结果：蛋白C基因（PROC）启动子C5156T杂合突变、2号外显子区域存在A6578T杂合突变。给予抗凝、溶栓、滤器植入等治疗，症状好转出院。②例2，女，32岁。临床诊断：双下肢深静脉血栓，双上、下肢缺血，双下肢皮肤软组织感染。PC：C27％，PS：C22．9％，AT：C86．7％。基因检测结果：PROC基因启动子C5156T杂合突变、A5045T杂合突变。给予抗凝、抗感染等治疗，因呼吸衰竭、感染性休克、DIC死亡。③例3，女，28岁。临床诊断：右髂静脉及股深静脉血栓。PC：C58％，PS：C57．3％，AT：C80．8％。基因检测结果：PROC启动子C4867T杂合突变，7号外显子12702-12704AGA（Arg192）或12705—12707AGA（Arg193）杂合缺失，9号外显子G15240A杂合突变。给予抗凝、溶栓、滤器植入等治疗，症状好转出院。④例4，男，30岁。临床诊断：左下肢深静脉血栓，双下肺动脉栓塞伴双下肺梗死。PC：C50％，PS：C75．0％，AT：C89．1％。基因检测结果：PROC启动子C4867T纯合突变、G4880A纯合突变和A5045T杂合突变，2号外显子T6589C杂合突变。给予抗凝、溶栓、滤器植入等相关治疗，症状好转出院。⑤多态性分析：PROC基因启动子C4867T杂合突变、G4880A纯合突变、C5156T杂合突变为PROC启动子多态性位点。结论PROC启动子多态性位点G4880A、C4867T、C5156T，错义突变A5045T、A6578T、G15240A，缺失突变AGA12702—12704del或12705-12707del可能与蛋白C缺陷症有关。PROC启动子错义突变A5045T、A6578T、G15240A，缺失突变AGA12702-12704del或12705-12706del是国际首次报告。Objective To investigate the molecular etiology of protein C （PC） deficiency. Methods Routine diagnosis and genetic analysis were performed on four probands with PC deficiency. Results （1）Case 1, female, 40 years old, diagnosed of deep vein thrombosis in left lower limb. PC activity （PC： C） was 48%, PS activity （PS： C） was 26.3%, AT activity （AT： C） was 75.6%. Genetic analysis discovered heterozygous mutation C5156T on promoter of PC gene, together with heterozygous mutation A6578T on Exon2 of PC gene. After anticoagulant, thrombolysis and filter implantation therapies, the patient went home with improvement. （2）Case 2, female, 32 years old, diagnosed of deep vein thrombosis in both lower limb, ischemia in both lower and upper limb, and skin infection in both lower limb. PC ： C 27%, PS： C 22.9%, AT： C 86.7%. Genetic analysis identified heterozygous mutation C5156T, together with heterozygous mutation A5045T on promoter of PC gene. After anticoagulant and anti-infection therapy, the patient died of respiratory failure, septic shock and DIC. （3）Case 3, female, 28 years old, diagnosed of vein thrombosis in right iliac and femoral vein. PC： C 58%, PS： C 57.3%, AT： C 80.8%. Genetic analysis disclosed heterozygous mutation C4867T on promoter of PC gene, AGA 12702- 12704del or 12705- 12707del on Exon7, the latter one lead to Arg192 or 193del. Heterozygous mutation G15240A on Exon9 was also found. After anticoagulant, thrombolysis and filter implantation therapies, the patient went home with improvement. （4）Case 4, male, 30 years old, diagnosed of vein thrombosis in right iliac and femoral vein. PC：C 50%, PS：C 75.0%, AT：C 89.1%. Genetic analysis found homozygous mutation C4867T and G4880A on promoter of PC gene, heterozygous mutation A5045T on promoter and heterozygous mutation T6589C on Exon2. After anticoagulant, thrombolysis and filter implantation therapies, the patient went home with improvement. （5）Polymorphism analysis revealed that heterozygous mutation

关 键 词：蛋白质C缺乏 静脉血栓形成 基因检测 多态性 单核苷酸 

分 类 号：R596.1[医药卫生—内科学] R440[医药卫生—临床医学]