ObjectiveTo investigate clinical characteristics and genetic mutations pathogenesis of a hereditary coagulation factor Ⅴ deficiency (HFⅤD) patient with infertility, and review the related literatures.
MethodsOne 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).
ResultsResults 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.
ConclusionsA 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.
