目的:探讨遗传性凝血因子Ⅴ缺乏症(HFⅤD)合并不孕症患者的临床特征及其基因突变致病机制，并进行相关文献复习。方法:选择2019年4月江苏省人民医院血液科收治的1例37岁HFⅤD合并不孕症患者为先证者。对本例先证者及其父母进行凝血功能相关实验室检查，以及止血和血栓遗传性疾病相关基因的二代基因测序(NGS)。本研究对本例先证者随访截至2020年6月30日。采用回顾性分析方法，收集本例先证者的临床病例资料，并对其临床特征进行分析。此外，以“凝血因子Ⅴ缺乏”“活化蛋白C抵抗”“factor Ⅴdeficiency”“activated protein C resistance”为中、英文关键词，检索中国知网数据库、万方数据知识服务平台及PubMed数据库中HFⅤD相关文献。检索时间设定为数据库建库至2020年7月31日。总结与本研究先证者相关的F5基因、PROC基因突变类型，以及该病患者的临床表现等。本研究取得先证者及其父母知情同意，签署临床研究知情同意书，并经江苏省人民医院伦理委员会审批通过(批准文号：2020-QT-13)。结果:对本例先证者的研究结果如下。①病史采集：因凝血功能异常合并不孕症于2019年4月至江苏省人民医院血液科就诊，其婚后正常性生活11年未孕，平素无明显出血症状。其父母均无出血症状。②实验室检查结果：活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、FⅤ∶C、蛋白C活性分别为34.2 s、15.7 s、21.1%和60.7%，均在正常参考值范围内。其父、母FⅤ∶C分别为36.1%和29.8%。③NGS检测结果显示，存在2个F5基因杂合突变，分别为10号外显子剪接突变c.1611＋2T>C和13号外显子错义突变c.2032A>G，以及1个2号染色体PROC基因9号外显子区域杂合突变c.970G>A。最终，本例先证者被诊断为HFⅤD合并不孕症。鉴于先证者及其父母无出血病史，遂对其HFⅤD未予特殊治疗。截至随访结束，先证者一般情况尚可。本研究文献复习显示，15篇文献纳入研究的82例HFⅤD患者发生F5基因突变，并且主要发生在5、8、10、13、14、15、17、23号外显子，其中以13号外显子最常被累及。本例及文献报道的HFⅤD患者的临床出血症状与FⅤ∶C水平、F5基因突变位点及类型无明显相关性。关于PROC基因突变的报道亦较常见，但是未见单纯蛋白C缺乏引起不孕症的报道。结论:本研究发现1个HFⅤD的新F5基因突变位点。F5基因杂合突变多导致HFⅤD患者FⅤ∶C轻度下降，患者通常无明显的出血表现，无需针对HFⅤD进行特殊治疗。但是，该结论仅限于对单一病例的临床分析，尚需要扩大样本量，进一步研究、验证。“,”Objective:To investigate clinical characteristics and genetic mutations pathogenesis of a hereditary coagulation factor Ⅴ deficiency (HFⅤD) patient with infertility, and review the related literatures.Methods:One case of HFⅤD patient with infertility who was admitted at Jiangsu Province Hospital in April, 2019 was selected as proband. Laboratory tests of coagulation function and next generation sequencing (NGS) of genes associated with hereditary diseases of thrombosis and haemostasis were performed on the proband and her parents.Follow-up was conducted until June 30, 2020. Retrospective analysis method was conducted to collect the clinical data of the proband, and to analyze her clinical manifestations. In addition, articles about HFⅤD in China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, and PubMed database were searched by the key words of “ factor Ⅴ deficiency” and “ activated protein C resistance” in Chinese and English. Retrieval time is from the database inception to July 31, 2020. Gene mutation of F5, PROC genes and clinical manifestations of patients related to this study were summarized. Informed consents of the proband and her parents were obtained and signed, and this study was approved by Ethics Committee of Jiangsu Province Hospital (Approval No. 2020-QT-13).Results:Results of researches on the proband were as follows. ① Medical history of the proband: the proband was admitted to Jiangsu Province Hospital due to coagulation abnormalities and infertility. She had normal sex life after marriage, and was sterile for 11 years. The proband usually has no bleeding symptoms. Neither of her parents showed bleeding symptoms.② Laboratory tests results showed, activated partial thromboplastin time (APTT), prothrombin time (PT), FⅤ∶C, and protein C of the proband were 34.2 s, 15.7s, 21.1% and 60.7%, respectively. Rest results of laboratory tests were normal. FⅤ∶C of her father and mother were 36.1% and 29.8%, respectively.③ NGS test results showed, proband present two heterozygous mutations of F5 gene, one was c. 1611+ 2T>C mutation in exon 10, the other one was c. 2032A>G mutation in exon 13.Mutation of c. 970G>A in exon 9 of PROC gene was also found in the proband. At last, the proband was diagnosed as HFⅤD comorbid with infertility. FⅤ deficiency was untreated, in view of the proband and her parents without bleeding symptoms. At the end of follow-up, general condition of the proband was good. Results of literatures review showed that FⅤ gene mutation of 82 cases of HFⅤD reported in 15 literatures patients occurs mainly in exon 5, 8, 10, 13, 14, 15, 17 and 23, of which exon 13 was the most often affected. Bleeding symptoms in HFⅤD were not related to the decreased FⅤ∶C, site and type of gene mutations of this case and patients with HFⅤD reported in literatures. There were many reports of PROC gene mutations, but none showed infertility caused by simple deficiency of protein C.Conclusions:A new mutation of F5 gene in HFⅤD was found. FⅤ∶C was decrease slightly in most cases with heterozygous mutations of F5 gene, which were usually with no significant bleeding symptoms and had no need for special treatment. However, this conclusion was limited to the clinical analysis of a single case. It′s still necessary to expand the sample size for further study and verification.