关键词：遗传性蛋白C缺乏；基因突变；深静脉血栓
本课题受国家自然科学基金(39300059)资助
摘要 目的： 研究一家族性血栓病相关病因的表型及基因型。方法： 先证者、其母、二 兄分别在35，19，33岁起无明显诱因患反复性下肢深静脉血栓(DVT)。对其四代13个家庭成 员的抗凝血酶Ⅲ、蛋白C(PC)、蛋白S(PS)、纤溶酶原的抗原和活性及活化的PC抗性等进行 检测。结果： 该家族5个成员患有Ⅰ型杂合子PC缺乏症(PC抗原和活性降低50%左右)。PC基 因各外显子及外显子、内含子连接区聚合酶链反应-单链构象多态性(PCR-SSCP)未发现明显的 异常带;亚克隆后测序发现PC的第Ⅵ外显子3444C→A导致134His→Asn变异,这是国外尚 未报道的新突变,被命名为PC长沙。此突变使限制性内切酶HphⅠ位点丧失,用PCR/HphⅠ 进行家系分析,证实了6个家系成员(包括5个PC缺乏者)具有同样的突变。结论： His134As n是此家族PC缺乏所致DVT的密切相关病理基因型。
TypeⅠ protein C deficiency caused by a novel protein C gene mutation Zheng Yanzhen ,Zhu Dinger,Zhou Botong. Research Center of Molecular B iology,Hunan Medical University,Changsha 410078
Abstract Objective: To study the phenotype and genotype of a throm bophilia family. Methods: Antigens and activities of protein C,antit hrombin Ⅲ,protein S,plasminogen and activated protein C resistance w ere assayed in 13 members from four generations of the family. Results: TypeⅠ protein C deficiency was revealed in 5 members including the 3 mem bers with deep vein thrombosis.All the exons and intron/exon junction s of the protein C gene were amplified by PCR.No abnormal band was found i n SSCP assay.DNA sequencing identified a novel mutation 3444C→A in exo n Ⅵ of protein C gene leading to His134Asn.This mutation erased a Hph Ⅰ s ite.PCR/HphⅠ analysis demonstrated that 6 members including 5 protei n C deficiency members had the same mutations. Conclusion: His134Asn i s a novel mutation causing type Ⅰ protein C deficiency.
Key words Hereditary protein C deficiency Gene mutation De ep vein thrombosis
自发性深静脉血栓(DVT)在西方发病率为1/1000 [1] ,其中10%～15%的血栓病与抗凝 血酶Ⅲ(ATⅢ)、蛋白C(PC)、蛋白S(PS)、纤溶酶原(Plg)等的遗传性缺乏相关 [2] ,2 0%～40%患者与活化的蛋白C抗性(APCR),即凝血因子Ⅴ(FⅤ)的遗传性变异相关 ......
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