遗传性抗凝血酶及遗传性蛋白C联合缺乏症家系研究

Research on a pedigree of hereditary antithrombin deficiency combined with hereditary protein C deficiency

目的:通过对遗传性抗凝血酶(AT)及遗传性蛋白C(PC)联合缺乏症先证者及其家属进行PC、蛋白S和AT相关活性及抗原检测,并进行基因测序分析,探讨遗传性AT及遗传性PC缺乏的危害和防治。方法:对先证者及其家属的血样,采用发色底物法进行AT及PC活性检测,采用ELISA法进行AT及PC抗原检测,采用PCR技术扩增后进行相关基因测序分析。结果:先证者及其母亲AT活性和抗原降低,经基因检测存在c.1066_1083del(p.Arg356_Phe361del)突变;先证者及其父亲PC活性和抗原降低,经基因检测存在c.842A>T(g.14983A>T;p.Asp281Val)突变。结论:发现AT及PC活性降低,及时进行分子学病因诊断,根据结果给予适当抗凝治疗及监测,达到预防血栓再发的良好效果。对先证者可制定长期抗凝治疗方案;对存在抗凝因子突变的携带者,在预防静脉血栓方面有提示意义。

Objective：To investigate the prophylaxis and treatment of hereditary antithrombin（AT）deficiency combined with hereditary protein C（PC）deficiency,we tested the activity,antigen concentration and gene sequencing of PC,PS and AT from the proband and his relatives.Method：Blood sample were obtained from the proband and his relatives,the activity of AT and PC were measured by chromogenic substrate method.Enzyme-linked immunosorbent assay（ELISA）was used to measure the antigen concentration of AT and PC.PCR and gene sequencing were employed for mutation analysis.Result：The activity and antigen concentration of AT decreased in the proband and his mother,genetic tests showed a novel SERPINC1 mutation c.1066_1083del（p.Arg356_ Phe361del）.The activity and antigen concentration of PC decreased in the proband and his father,genetic tests showed a novel PROC mutation c.842A〉T（p.Asp281Val）.Conclusion：Early diagnosis and molecular analysis of AT and PC deficiency,in combination with appropriate anticoagulant treatment and monitoring,could make contribution to prevent thrombosis recurrence.And it would be a reminder for mutation carriers to prevent venous thrombosis.