目的:对1个遗传性凝血因子Ⅺ(coagulation factor FⅪ，FⅪ)缺陷症患者家系进行临床表型和基因变异分析，寻找致病变异并初步探讨其分子机制。方法:在Stago全自动血凝仪上检测先证者及其家系成员(共3代6人)活化部分凝血活酶时间(activated partial thromboplastin time，APTT)等血凝相关检测项目，FⅪ活性(FⅪ activity，FⅪ∶C)及其他有关凝血因子的活性；用ELISA法检测FⅪ抗原(FⅪ antigen，FⅪ∶Ag)。提取基因组DNA，用Sanger测序法测定n F11基因所有外显子及侧翼序列；用ClustalX-2.1-win软件分析变异氨基酸的保守性；用MutationTaster在线生物信息学软件分析变异是否有害；用Swiss-Pdb Viewer模型分析软件分析变异氨基酸对蛋白结构的影响。n 结果:先证者APTT明显延长，为94.2 s；FⅪ∶C和FⅪ∶Ag分别降低为1%和1.3%；先证者父亲、母亲、儿子和女儿APTT分别为42.1 s、43.0 s、42.5 s和41.0 s，FⅪ∶C和FⅪ∶Ag均降低至正常值的一半左右；先证者丈夫APTT、FⅪ∶C和FⅪ∶Ag均正常。测序结果显示先证者n F11基因存在第10外显子c.1103G>A(p.Gly350Glu)杂合错义变异和第13外显子c.1556G>A(p.Trp501stop)杂合错义变异。先证者父亲和女儿携带p.Gly350Glu杂合错义变异；母亲和儿子携带p.Trp501stop杂合无义变异。保守性分析表明Gly350和Trp501在同源物种间高度保守。MutationTaster在线生物信息学软件对两个变异的预测结果均为“disease causing”，表明变异有害。蛋白模型分析表明，p.Gly350Glu变异影响了蛋白质的结构及稳定性。n 结论:p.Gly350Glu和p.Trp501stop复合杂合变异可能是该家系遗传性FⅪ缺陷症的分子发病机制。“,”Objective:To analyze the clinical phenotype and genetic basis for a Chinese pedigree affected with coagulation factor Ⅺ (FⅪ) deficiency.Methods:Activated partial thromboplastin time (APTT) and other blood coagulation factors, FⅪ activity (FⅪ∶C) and other relevant coagulation factor activities for a large Chinese pedigree including 6 patients from 3 generations were determined on a Stago automatic coagulometer. The FⅪ antigen (FⅪ∶Ag) was determined with an ELISA method. All exons and flanking regions of the n F11 gene were subjected to Sanger sequencing. ClustalX-2.1-win software was used to analyze the conservation of amino acids. Pathogenicity of the variants was predicted with Mutation Taster online bioinformatics software and Swiss-Pdb Viewer.n Results:The APTT of the proband was prolonged to 94.2 s. The FⅪ∶C and FⅪ∶Ag were decreased to 1% and 1.3%, respectively. The APTT of her father, mother, son and daughter was 42.1 s, 43.0 s, 42.5 s and 41.0 s, respectively. The FⅪ∶C and the FⅪ∶Ag of them were almost half of the normal values. The APTT, FⅪ∶C and FⅪ∶Ag of her husband were all normal. Genetic testing revealed that the proband has carried a heterozygous missense c. 1103G>A (p.Gly350Glu) variant in exon 10 and a heterozygous missense c. 1556G>A (p.Trp501stop) variant in exon 13 of then F11 gene. The father and daughter were heterozygous for the c. 1103G>A variant, whilst the mother and son were heterozygous for the c. 1556G>A variant. Both Gly350 and Trp501 are highly conserved among homologous species, and both variants were predicted to be “ disease causing” by Mutation Taster. Protein modeling indicated there are two hydrogen bonds between Gly350 and Phe312 in the wild-type, but the p. Gly350Glu variant may add a hydrogen bond to Glu and Tyr351 and create steric resistance between the two, both may affect the structure and stability of protein.n Conclusion:The c. 1103G>A and c. 1556G>A compound heterozygous variants probably underlay the pathogenesis of congenital FⅪ deficiency in this pedigree.