1例复合杂合突变导致遗传性凝血因子Ⅺ缺陷症的分子致病机制  

Molecular mechanism analysis of a family with hereditary coagulation FⅪdeficiency caused by compound heterozygous mutations

作　　者：陈元 秦朗译 林双女 杨丽红[1] 张柯 叶龙颖 金艳慧[1] 王明山[1] Chen Yuan;Qin Langyi;Lin Shuangnyu;Yang Lihong;Zhang Ke;Ye Longying;Jin Yanhui;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,温州325015

出　　处：《中华血液学杂志》2024年第3期294-298,共5页Chinese Journal of Hematology

基　　金：温州市公益科技基金(Y2020110);浙江省检验诊断及转化研究重点实验室(2022E10022)。

摘　　要：1例34岁女性患者因“乳房结节”拟行手术切除,术前检查发现活化部分凝血活酶时间(APTT)66.2 s、凝血因子Ⅺ活性(FⅪ∶C)2%、FⅪ抗原(FⅪ∶Ag)40.3%,患者及家系成员均无异常出血表现。诊断为遗传性凝血因子Ⅺ缺陷症。基因检测发现其F11基因第10外显子c.1107C>A(p.Tyr351stop)杂合无义突变、第13外显子c.1562A>G(p.Tyr503Cys)杂合错义突变,其父亲和儿子为p.Tyr351stop突变的杂合携带者,而母亲和女儿为p.Tyr503Cys突变的杂合携带者。体外表达结果显示,p.Tyr351stop突变导致F11基因转录水平显著降低,而p.Tyr503Cys突变对F11基因转录水平以及蛋白表达水平无影响,但该突变导致细胞培养上清液中FⅪ∶C水平显著降低。A 34 year old female patient was scheduled to undergo surgical resection due to a"breast nodule".Preoperative examination revealed an activated partial thromboplastin time(APTT)of 66.2 seconds,coagulation factorⅪactivity(FⅪ:C)of 2%,and FⅪantigen(FⅪ:Ag)of 40.3%.The patient and family members showed no abnormal bleeding symptoms.Diagnosed as hereditary coagulation factorⅪdeficiency.Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10,c.1107C>A(p.Tyr351stop),and a heterozygous missense mutation in exon 13,c.1562A>G(p.Tyr503Cys).The father and son were p Heterozygous carriers of Tyr351stop mutation,while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations.The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene,while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene,but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.

关 键 词：遗传性凝血因子Ⅺ缺陷症 异常出血 家系成员 无义突变 携带者 凝血因子Ⅺ 基因检测 分子致病机制 

分 类 号：R73[医药卫生—肿瘤]