凝血因子Ⅺ基因变异致下消化道出血病因分析  

Analysis of lower gastrointestinal bleeding caused by FⅪ gene mutation

作　　者：王欢欢[1] 刘媚娜[1] 谢海啸[1] 贾恺琦 曾蔓霖 王明山[1] WANG Huanhuan;LIU Meina;XIE Haixiao;JIA Kaiqi;ZENG Manlin;WANG Mingshan(Department of Clinical Laboratory,Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]温州医科大学附属第一医院,医学检验中心,浙江省检验诊断及转化研究重点实验室,浙江温州325015

出　　处：《温州医科大学学报》2022年第4期288-293,共6页Journal of Wenzhou Medical University

基　　金：温州市基础性科研项目(Y2020110)。

摘　　要：目的:对1例遗传性凝血因子Ⅺ(FⅪ)缺陷症患者行内镜下直肠息肉摘除术后出现下消化道异常出血进行病因分析,探讨FⅪ基因变异与治疗后下消化道出血的关系。方法:家系调查(共3代5人)。检测患者及其家系成员相关凝血指标。提取外周血基因组DNA进行PCR扩增,采用DNA直接测序法分析患者FⅪ基因的全部外显子、侧翼序列、5’和3’端非翻译区序列,及家系成员相应的变异位点区域。用PyMol软件构建基因变异前后蛋白模型。结果:患者因“直肠息肉摘除术后3 d,血便2 d”入院。凝血指标检查显示患者的活化部分凝血活酶时间(APTT)、FⅪ活性(FⅪ:C)和FⅪ抗原(FⅪ:Ag)分别为50.9 s、53%和47.2%;其父亲上述3项指标分别为45.4 s、44%和43.1%。DNA测序发现患者及其父亲的FⅪ基因第8号外显子均存在c.841C>T杂合无义变异(p.Gln281*)。蛋白模型分析显示p.Gln281*变异会产生截短蛋白。结论:该家系FⅪ基因第8号外显子c.841C>T(NM_000128)杂合无义变异与其FⅪ水平减低有关,可能也是该患者行内镜下直肠息肉摘除术后出现下消化道异常出血的主要原因。Objective: To analyze the pathogenesis of abnormal lower gastrointestinal bleeding after endoscopic rectal polypectomy in a patient with hereditary coagulation factor Ⅺ(FⅪ) deficiency, and to explore the relationship between the FⅪ mutation and lower gastrointestinal bleeding after treatment. Methods: Pedigree investigation(5 people of 3 generations in total) was made and relevant coagulation factor indexes of the patient and her family members were detected. Genomic DNA of peripheral blood was extracted for PCR amplification.All the exons, flanking sequences, 5’ and 3’ untranslated regions of FⅪ gene of the patient were analyzed by direct sequencing. And the corresponding mutation site was subjected to sequencing in other family members.The PyMol software was used to construct protein model before and after gene mutation. Results: The patient was admitted to hospital for abnormal lower gastrointestinal bleeding after endoscopic rectal polypectomy. The activated partial thromb oplastin time(APTT), FⅪ activity(FⅪ:C) and FⅪ antigen(FⅪ:Ag) of the patient was 50.9 s, 53% and 47.2%, respectively;The above three indicators for her father were 45.4 s, 44% and 43.1%,respectively. Gene sequencing revealed that the patient and her father had a heterozygous nonsense mutation c.841C>T(p.Gln281*) in exon 8 of the FⅪ gene. Protein model analysis demonstrated that the p.Gln281*mutation producing truncated protein. Conclusion: A heterozygous nonsense mutation c.841C>T(NM_000128)in exon 8 of the FⅪ gene is responsible for the low FⅪ level in this pedigree, which might be the main reason for abnormal lower gastrointestinal bleeding after endoscopic rectal polypectomy in this patient.

关 键 词：遗传性凝血因子Ⅺ缺陷症 基因变异 内镜下治疗 下消化道出血 

分 类 号：R554[医药卫生—血液循环系统疾病]