7例遗传性凝血因子Ⅺ缺陷症患者基因型与临床表型分析  

Analysis of genotype and clinical phenotype of 7 patients with hereditary factor Ⅺ deficiency

作　　者：翁妙珊 杨立业 吴教仁 章金灿 袁炜嗣 庄丹 林芬 WENG Miaoshan;YANG Liye;WU Jiaoren;ZHANG Jincan;YUANWeisi;ZHUANG Dan;LIN Fen(Clinical laboratory,Chaozhou Central Hospital Affiliated to Southern Medical University,Chaozhou,Guangdong,China,521000;Central Laboratory,Chaozhou Central Hospital Affiliated to Southern Medical University,Chaozhou,Guangdong,China,521000;Department of General Surgery I,Chaozhou Central Hospital Affiliated to Southern Medical University,Chaozhou,Guangdong,China,521000)

机构地区：[1]南方医科大学附属潮州中心医院检验科,广东潮州521000 [2]南方医科大学附属潮州中心医院中心实验室,广东潮州521000 [3]南方医科大学附属潮州中心医院普外一科,广东潮州521000

出　　处：《分子诊断与治疗杂志》2021年第7期1130-1133,共4页Journal of Molecular Diagnostics and Therapy

基　　金：潮州市卫生健康局科研项目(2019042);潮州市科技计划项目(2019ZC18)。

摘　　要：目的分析7例遗传性凝血因子Ⅺ(FⅪ)缺陷症患者的基因突变类型与临床表型。方法采用一期法检测患者FⅪ活性(FⅪ:C),免疫火箭电泳法检测FⅪ抗原(FⅪ:Ag)水平,并抽提患者外周血DNA,PCR扩增患者FⅪ基因所有的外显子及其侧翼序列,DNA直接测序进行基因分析。结果在7例遗传性FⅪ缺陷症患者中共发现5种基因突变,包括3种无义突变(p.Lys327X、p.Tyr351X、p.Gln263X),1种移码突变(p.Leu424fsX10)和1种剪接位点突变(c.326-1G>A);除患者7为单杂合突变,FⅪ:C为56.7%,FⅪ:Ag59.2%,其余患者FⅪ:C和FⅪ:Ag均明显降低(<2%和<1%),基因型为纯合突变或复合杂合突变;患者临床出血表现轻重不一,患者1、2均有术后出血不止的表现,而患者5则无术后出血表现。结论所发现的5种基因突变是导致7例遗传性FⅪ缺陷症患者的分子发病机制,其中p.Gln263X较常见,p.Lys327X为新发现的FⅪ基因突变类型,而FⅪ:C与患者的临床表型之间无明显相关性。Objective To analyze the clinical phenotype and genotype of seven patients with hereditary coagulation factor Ⅺ(FⅪ)deficiency. Methods FⅪ activity(FⅪ:C)was measured by one-stage assay and the level of FⅪ antigen(FⅪ:Ag)was detected by immuno-rocket electrophoresis. The patient.s peripheral blood DNA was extracted,and all exons and their flanking sequences of the FⅪ gene were amplified by PCR and followed by DNA sequencing. A total of 5 gene mutations were found in 7 patients with hereditary FⅪ deficiency,including 3 nonsense mutations(p.Lys327 X,p.Tyr351X,p.Gln263 X),1 frameshift mutation(p.Leu424 fsX10) and 1 splicing Site mutation(c.326-1 G>A). Except for the patient 7 with a single heterozygous mutation(FⅪ:C 56.7%,FⅪ:Ag 59.2%),and the rest of patients had extremely low FⅪ:C and FⅪ:Ag( <2% and <1% respectively). The genotype of patients was homozygous or compound heterozygous mutation. The clinical bleeding of patients varies from severity to severity. Patients 1 and 2 have postoperative bleeding,while patient 5 has no postoperative bleeding. Conclusion The five gene variations found are the molecular pathogenesis of 7 patients with hereditary FⅪ deficiency. Among them,p.Gln263 x is more common,p.Lys327 x is the newly discovered FⅪ gene mutation type. There is no significant correlation between FⅪ:C and clinical phenotype.

关 键 词：凝血因子Ⅺ 基因型 突变 临床表型 

分 类 号：R596[医药卫生—内科学]