蛋白C基因新突变His134Asn所致Ⅰ型蛋白C缺乏症

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：Ｈｉｓ１３４Ａｓｎ是此家族ＰＣ缺乏所致ＤＶＴ的密切相关病理基因型。

Type I protein C deficiency caused by a novel protein C gene mutation]

OBJECTIVE: To study the phenotype and genotype of a thrombophilia family. METHODS: Antigens and activities of protein C, antithrombin III, protein S, plasminogen and activated protein C resistance were assayed in 13 members from four generations of the family. RESULTS: Type I protein C deficiency was revealed in 5 members including the 3 members with deep vein thrombosis. All the exons and intron/exon junctions of the protein C gene were amplified by PCR. No abnormal band was found in SSCP assay. DNA sequencing identified a novel mutation 3444C-->A in exon VI of protein C gene leading to His134Asn. This mutation erased a Hph I site. PCR/Hph I analysis demonstrated that 6 members including 5 protein C deficiency members had the same mutations. CONCLUSION: His134Asn is a novel mutation causing type I protein C deficiency.