Objective: To test the anticoagulation functions, perform the genetic diagnosis and analyze the clinical characteristics in a family with combined heterozygous genetic variants of PROC and PROS1.
Methods: Peripheral blood was collected from all the family members. Hematological phenotypes and activity of anticoagulant factors were analyzed. Target genes were amplified by PCR from DNA isolated from peripheral blood, and then were analyzed by Sanger DNA sequencing.
Results: Many members in the family displayed the combined genetic variants in protein C and protein S, and six family members accompanied by deep venous thrombosis (DVT). The influences of genetic and secondary factors on the incidence of venous thrombosis in the family members were analyzed. The results showed that in this family, carriers of combined protein C and protein S gene defects had a higher incidence of VTE, but acquired factors still played a key role in the eventual thrombotic symptoms.
Conclusion: Venous thromboembolism (VTE) is a multifactorial disease, the combined genetic heterozygous mutations of protein C and S is an important genetic factor, and the clinical phenotype show a high heterogenicity, the secondary factors contribute to the VTE incidence.
题目: 家族性蛋白C与蛋白S基因联合杂合突变家系的基因变异特点与临床特征分析.
目的: 对1个蛋白C和蛋白S基因联合杂合突变的家系进行各项抗凝功能检测、基因诊断及临床特征分析.
方法: 采集家族成员外周血，分析各项出凝血指标和血浆抗凝蛋白活性，采用聚合酶链反应、双脱氧链终止DNA测序法（Sanger测序法）检测基因突变.
结果: 在该家系中发现多人为遗传性蛋白C与蛋白S联合杂合突变，其中6位家族成员伴有深静脉血栓症状。结合家族中各成员的相关基因变异特点和临床表现，分析了遗传因素和继发性因素对该家系成员静脉血栓发病的影响。结果显示该家系中，蛋白C与蛋白S基因联合缺陷携带者有更高的静脉血栓发生率，但后天继发性因素仍对其最终是否出现血栓症状起重要作用.
结论: 静脉血栓形成是多因素导致的疾病，蛋白C合并蛋白S基因联合杂合突变是重要的遗传因素，临床上具有较大的异质性，继发性因素使静脉血栓栓塞症的发生率提高.