本文選題：抗凝蛋白缺陷　切入點：血栓形成　出處：《廣西醫(yī)科大學》2017年碩士論文

【摘要】：目的研究3個遺傳性抗凝血蛋白缺陷致血栓形成家系臨床表型及基因突變。方法收集抗凝血蛋白缺陷致血栓形成家系病史資料,分析患者及其家族成員的臨床表現(xiàn)及輔助檢查結果。采集先證者及其家族成員血樣5ml置入1:9枸櫞酸鈉抗凝管中,采用發(fā)光底物法對先證者和家族成員進行蛋白C(PROC)活性、蛋白S(PROS)活性、抗凝血酶(AT)III活性進行測定;乙二胺四乙酸抗凝外周血提取基因組DNA,采用DNA直接測序法對先證者PROC、PROS1等相關基因進行基因檢測。根據(jù)先證者的基因檢測結果,對家族其他成員針對突變基因進行基因檢測。結果家系一先證者(III-10)及其他3位家庭成員(II-5、II-6、III-9)、家系二先證者(II-3)及其他3位家庭成員(I-1、I-2、III-1)、家系三先證者(II-1)及其他1位無臨床表現(xiàn)家庭成員(I-1)PROC基因第7外顯子,c.565CT(編碼區(qū)第565號核苷酸由胞嘧啶變異為胸腺嘧啶),導致氨基酸改變(第189號氨基酸由精氨酸變?yōu)樯彼?。家系一先證者(III-10)診斷為“顱內靜脈竇血栓形成”,父親(II-5)表現(xiàn)為“下肢腫脹、疼痛”。家系二先證者(II-3)診斷為“顱內靜脈竇血栓形成”,父親(I-1)診斷為“左下肢深靜脈血栓形成”。此外,家系一先證者(III-10)及6位家庭成員(II-5、II-7、II-9、II-10、III-9、III-15)的PROS1基因還發(fā)現(xiàn)兩種突變,分別為(C-A)+520 to termination,導致氨基酸改變和c.2001AG(沒有氨基酸替代)。其中,家系一成員(III-15)被診斷為“乆靜脈血栓形成”。結論本次研究發(fā)現(xiàn)在三個家系中存在PROC基因第7外顯子,c.565CT突變。它可能是導致3個家系先證者蛋白C活性下降及靜脈血栓形成的主要原因。本研究在國內外首次報道了純合子PROC(c.565CT)突變致青年缺血性卒中的病例。家系一中還發(fā)現(xiàn)PROS1基因(C-A)+520 to termination和c.2001AG突變,這兩種突變可能會對蛋白S活性水平有影響,從而增加血栓形成的風險。
[Abstract]:Objective to study the clinical phenotype and gene mutation in three families with hereditary anticoagulant protein deficiency.Methods the family history of thrombus caused by anticoagulant protein deficiency was collected and the clinical manifestations and auxiliary examination results of the patients and their family members were analyzed.The blood samples of probands and their family members were collected and placed into the 1:9 sodium citrate anticoagulant tube. The activity of protein Cnprocr, protein SfP, and the activity of antithrombin titer III were determined by luminescent substrate method.The genomic DNA was extracted from the peripheral blood of ethylenediamine tetraacetic acid anticoagulant, and the genes related to proctrin PROS1 and other genes were detected by DNA direct sequencing.Based on the results of the proband gene test, the other members of the family were tested for the mutant gene.Nucleotides 565 mutated from cytosine to thymine, resulting in changes in amino acids (amino acid 189 from arginine to tryptophan)."Intracranial venous sinus thrombosis" was diagnosed as "intracranial venous sinus thrombosis", and "swelling and pain in lower extremities" was found in father's II-5.II-3 was diagnosed as "intracranial venous sinus thrombosis" and father as "deep venous thrombosis of left lower extremity".In addition, two mutations were found in the PROS1 gene of the first proband and six family members, I. e., II-5, II-7, II-9, II-10, III-9, and III-15, respectively, which were identified as C-A520 to terminations, leading to amino acid changes and c.2001AG1 (no amino acid substitution).Among them, a family member of the III-15) was diagnosed as "vein thrombosis."Conclusion in this study, the mutation of exon 7 of PROC gene was found on c. 565CT in three families.It may be the main cause of the decrease of protein C activity and venous thrombosis in three families.This study reported for the first time a case of ischemic stroke caused by homozygous procter c. 565CT2 mutation at home and abroad.Family 1 also found mutations in the PROS1 gene (C-A) 520 to termination and c.2001AG, which may have an effect on protein S activity, thus increasing the risk of thrombogenesis.
【學位授予單位】：廣西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R596;R743.3

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