{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T23:32:44Z","timestamp":1774567964800,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Local University of Ferrara Grants (FAR and FIR)","award":["2020-2021"],"award-info":[{"award-number":["2020-2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Inherited thrombophilia (e.g., venous thromboembolism, VTE) is due to rare loss-of-function mutations in anticoagulant factors genes (i.e., SERPINC1, PROC, PROS1), common gain-of-function mutations in procoagulant factors genes (i.e., F5, F2), and acquired risk conditions. Genome Wide Association Studies (GWAS) recently recognized several genes associated with VTE though gene defects may unpredictably remain asymptomatic, so calculating the individual genetic predisposition is a challenging task. We investigated a large family with severe, recurrent, early-onset VTE in which two sisters experienced VTE during pregnancies characterized by a perinatal in-utero thrombosis in the newborn and a life-saving pregnancy-interruption because of massive VTE, respectively. A nonsense mutation (CGA &gt; TGA) generating a premature stop-codon (c.1171C&gt;T; p.R391*) in the exon 6 of SERPINC1 gene (1q25.1) causing Antithrombin (AT) deficiency and the common missense mutation (c.1691G&gt;A; p.R506Q) in the exon 10 of F5 gene (1q24.2) (i.e., FV Leiden; rs6025) were coinherited in all the symptomatic members investigated suspecting a cis-segregation further confirmed by STR-linkage-analyses [i.e., SERPINC1 IVS5 (ATT)5\u201318, F5 IVS2 (AT)6\u201333 and F5 IVS11 (GT)12\u201316] and SERPINC1 intragenic variants (i.e., rs5878 and rs677). A multilocus investigation of blood-coagulation balance genes detected the coexistence of FV Leiden (rs6025) in trans with FV HR2-haplotype (p.H1299R; rs1800595) in the aborted fetus, and F11 rs2289252, F12 rs1801020, F13A1 rs5985, and KNG1 rs710446 in the newborn and other members. Common selected gene variants may strongly synergize with less common mutations tuning potential life-threatening conditions when combined with rare severest mutations. Merging classic and newly GWAS-identified gene markers in at risk families is mandatory for VTE risk estimation in the clinical practice, avoiding partial risk score evaluation in unrecognized at risk patients.<\/jats:p>","DOI":"10.3390\/genes12060934","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T11:19:20Z","timestamp":1624015160000},"page":"934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cis-Segregation of c.1171C&gt;T Stop Codon (p.R391*) in SERPINC1 Gene and c.1691G&gt;A Transition (p.R506Q) in F5 Gene and Selected GWAS Multilocus Approach in Inherited Thrombophilia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-6120","authenticated-orcid":false,"given":"Donato","family":"Gemmati","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Centre Haemostasis & Thrombosis, University of Ferrara, 44121 Ferrara, Italy"},{"name":"University Center for Studies on Gender Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1107-2419","authenticated-orcid":false,"given":"Giovanna","family":"Longo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Franchini","sequence":"additional","affiliation":[{"name":"Centre Haemostasis & Thrombosis, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-6785","authenticated-orcid":false,"given":"Juliana","family":"Araujo Silva","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Lunghi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Moratelli","sequence":"additional","affiliation":[{"name":"Centre Haemostasis & Thrombosis, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iva","family":"Maestri","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luisa","family":"Serino","sequence":"additional","affiliation":[{"name":"Centre Haemostasis & Thrombosis, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-066X","authenticated-orcid":false,"given":"Veronica","family":"Tisato","sequence":"additional","affiliation":[{"name":"University Center for Studies on Gender Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Department of Translational Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1055\/s-0038-1650289","article-title":"Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency","volume":"75","author":"Reitsma","year":"1996","journal-title":"Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/00001721-199803000-00008","article-title":"Coexistence of antithrombin deficiency, factor V Leiden and hyperhomocysteinemia in a thrombotic family","volume":"9","author":"Gemmati","year":"1998","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1160\/TH06-08-0440","article-title":"Coexistence of three genetic risk factors in a Spanish thrombophilic family: Factor V Leiden, prothrombin 20210 and a new type I antithrombin deficiency","volume":"97","author":"Ordonez","year":"2007","journal-title":"Thromb. Haemost."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1097\/00001721-200112000-00011","article-title":"The reduced sensitivity of the ProC Global test in protein S deficient subjects reflects a reduction in the associated thrombotic risk","volume":"12","author":"Gemmati","year":"2001","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_5","first-page":"99","article-title":"Coexistence of factor V G1691A and factor II G20210A gene mutations in a thrombotic family is associated with recurrence and early onset of venous thrombosis","volume":"31","author":"Gemmati","year":"2001","journal-title":"Haemostasis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0049-3848(98)00120-0","article-title":"A modified functional global test to measure protein C, protein S activities and the activated protein C-resistance phenotype","volume":"92","author":"Gemmati","year":"1998","journal-title":"Thromb. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/00001721-199703000-00006","article-title":"Resistance to activated protein C and low levels of protein S activity in nine thrombophilic families: A correct diagnosis","volume":"8","author":"Gemmati","year":"1997","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1177\/107602969700300304","article-title":"Different Anticoagulant Response to Activated Protein C (APC test) and to Agkistrodon Contortix Venom (ACV test) in a Family with FV-R506Q Substitution","volume":"3","author":"Gemmati","year":"1997","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1538-7836.2007.02450.x","article-title":"Incidence and mortality of venous thrombosis: A population-based study","volume":"5","author":"Naess","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"d813","DOI":"10.1136\/bmj.d813","article-title":"Risk of recurrence after venous thromboembolism in men and women: Patient level meta-analysis","volume":"342","author":"Douketis","year":"2011","journal-title":"BMJ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1161\/CIRCULATIONAHA.113.004768","article-title":"Sex difference in risk of second but not of first venous thrombosis: Paradox explained","volume":"129","author":"Roach","year":"2014","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gemmati, D., Varani, K., Bramanti, B., Piva, R., Bonaccorsi, G., Trentini, A., Manfrinato, M.C., Tisato, V., Care, A., and Bellini, T. (2019). \u201cBridging the Gap\u201d Everything that Could Have Been Avoided If We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010296"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1177\/1534734610384653","article-title":"Interplay of iron metallobiology, metalloproteinases, and FXIII, and role of their gene variants in venous leg ulcer","volume":"9","author":"Singh","year":"2010","journal-title":"Int. J. Low Extrem. Wounds"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"301","DOI":"10.4103\/0976-3147.102611","article-title":"Investigation of in vitro cytotoxicity of the redox state of ionic iron in neuroblastoma cells","volume":"3","author":"Singh","year":"2012","journal-title":"J. Neurosci. Rural Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1538-7836.2011.04311.x","article-title":"Lessons from genome-wide association studies in venous thrombosis","volume":"9","author":"Morange","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/gepi.21731","article-title":"A genome-wide association study for venous thromboembolism: The extended cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium","volume":"37","author":"Tang","year":"2013","journal-title":"Genet Epidemiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e001827","DOI":"10.1161\/CIRCGEN.117.001827","article-title":"Genome-wide association study identifies a novel genetic risk factor for recurrent venous thrombosis","volume":"11","author":"Germain","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1080\/17474086.2020.1804354","article-title":"Genetic risk factors for venous thromboembolism","volume":"13","author":"Zoller","year":"2020","journal-title":"Expert Rev. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Prandoni, P. (2005). Acquired risk factors for venous thromboembolism in medical patients. Hematol. Am. Soc. Hematol. Educ. Program.","DOI":"10.1182\/asheducation-2005.1.458"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e001060","DOI":"10.1161\/JAHA.114.001060","article-title":"Multilocus genetic risk scores for venous thromboembolism risk assessment","volume":"3","author":"Soria","year":"2014","journal-title":"J. Am. Hearth Assoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1399-0004.2011.01746.x","article-title":"Management of inherited thrombophilia: Guide for genetics professionals","volume":"81","author":"Varga","year":"2012","journal-title":"Clin. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1161\/CIRCULATIONAHA.109.192278","article-title":"Criteria for evaluation of novel markers of cardiovascular risk: A scientific statement from the American Heart Association","volume":"119","author":"Hlatky","year":"2009","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0140-6736(06)69110-1","article-title":"Effect of patient\u2019s sex on risk of recurrent venous thromboembolism: A meta-analysis","volume":"368","author":"McRae","year":"2006","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.thromres.2018.07.008","article-title":"The genetics of antithrombin","volume":"169","author":"Corral","year":"2018","journal-title":"Thromb. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1055\/s-0038-1650673","article-title":"Inherited thrombophilia: Part 2","volume":"76","author":"Lane","year":"1996","journal-title":"Thromb. Haemost."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1055\/s-0038-1650638","article-title":"Inherited thrombophilia: Part 1","volume":"76","author":"Lane","year":"1996","journal-title":"Thromb. Haemost."},{"key":"ref_27","first-page":"e32","article-title":"Genotype-phenotype gradient of SERPINC1 variants in a single family reveals a severe compound antithrombin deficiency in a dead embryo","volume":"191","author":"Palomo","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/j.1365-2141.1993.tb03142.x","article-title":"Identification of nine novel mutations in type I antithrombin deficiency by heteroduplex screening","volume":"84","author":"Chowdhury","year":"1993","journal-title":"Br. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1160\/TH11-09-0671","article-title":"Molecular analysis and genotype-phenotype correlation in patients with antithrombin deficiency from Southern Italy","volume":"107","author":"Castaldo","year":"2012","journal-title":"Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/j.biocel.2003.08.002","article-title":"Coagulation factor V","volume":"36","author":"Duga","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/369064a0","article-title":"Mutation in blood coagulation factor V associated with resistance to activated protein C","volume":"369","author":"Bertina","year":"1994","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1073\/pnas.90.3.1004","article-title":"Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C","volume":"90","author":"Dahlback","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1055\/s-0038-1650219","article-title":"Detection of new polymorphic markers in the factor V gene: Association with factor V levels in plasma","volume":"75","author":"Lunghi","year":"1996","journal-title":"Thromb. Haemost."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1182\/blood.V90.4.1552","article-title":"A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype","volume":"90","author":"Bernardi","year":"1997","journal-title":"Blood"},{"key":"ref_35","first-page":"629","article-title":"A missense mutation (Y1702C) in the coagulation factor V gene is a frequent cause of factor V deficiency in the Italian population","volume":"86","author":"Castoldi","year":"2001","journal-title":"Haematologica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1055\/s-0038-1650290","article-title":"Pseudo homozygous activated protein C resistance due to double heterozygous factor V defects (factor V Leiden mutation and type I quantitative factor V defect) associated with thrombosis: Report of two cases belonging to two unrelated kindreds","volume":"75","author":"Simioni","year":"1996","journal-title":"Thromb. Haemost."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1538-7836.2005.01572.x","article-title":"Inherited defects of coagulation Factor V: The thrombotic side","volume":"4","author":"Vos","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.3324\/haematol.2019.232587","article-title":"Profiling the mutational landscape of coagulation factor V deficiency","volume":"105","author":"Paraboschi","year":"2020","journal-title":"Haematologica"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1034\/j.1399-0004.2000.570409.x","article-title":"Association of the R485K polymorphism of the factor V gene with poor response to activated protein C and increased risk of coronary artery disease in the Chinese population","volume":"57","author":"Le","year":"2000","journal-title":"Clin. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.thromres.2019.04.004","article-title":"Molecular basis of SERPINC1 mutations in Japanese patients with antithrombin deficiency","volume":"178","author":"Tamura","year":"2019","journal-title":"Thromb. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1182\/blood-2011-12-397752","article-title":"Multiple SNP testing improves risk prediction of first venous thrombosis","volume":"120","author":"Bezemer","year":"2012","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/ajh.2830460210","article-title":"Genetic linkage studies in antithrombin-deficient kindreds using a highly polymorphic trinucleotide short tandem repeat (STR) within the human antithrombin gene","volume":"46","author":"Ni","year":"1994","journal-title":"Am. J. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1046\/j.1365-2141.2001.03052.x","article-title":"A highly polymorphic microsatellite in the factor V gene is an informative tool for the study of factor V-related disorders","volume":"114","author":"Castoldi","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1055\/s-0037-1613399","article-title":"A FV multiallelic marker detects genetic components of APC resistance contributing to venous thromboembolism in FV Leiden carriers","volume":"89","author":"Mingozzi","year":"2003","journal-title":"Thromb. Haemost."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e691","DOI":"10.7717\/peerj.691","article-title":"The physiologic and therapeutic role of heparin in implantation and placentation","volume":"3","author":"Quaranta","year":"2015","journal-title":"Peer. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1182\/blood.V94.8.2590.420k40_2590_2594","article-title":"Gene-gene and gene-environment interactions determine risk of thrombosis in families with inherited antithrombin deficiency","volume":"94","author":"Vandenbroucke","year":"1999","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1365-2141.2012.09121.x","article-title":"Candidate gene polymorphisms and the risk for pregnancy-related venous thrombosis","volume":"157","author":"Dahm","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0140-6736(05)80081-9","article-title":"Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study","volume":"342","author":"Koster","year":"1993","journal-title":"Lancet"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1001\/jama.293.6.715","article-title":"Malignancies, prothrombotic mutations, and the risk of venous thrombosis","volume":"293","author":"Blom","year":"2005","journal-title":"JAMA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/cge.12910","article-title":"Maternal genetic polymorphisms and unexplained recurrent miscarriage: A systematic review and meta-analysis","volume":"91","author":"Shi","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Loizidou, E.M., Kucherenko, A., Tatarskyy, P., Chernushyn, S., Livshyts, G., Gulkovskyi, R., Vorobiova, I., Antipkin, Y., Gorodna, O., and Kaakinen, M.A. (2021). Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study. Genes, 12.","DOI":"10.3390\/genes12010064"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.ajhg.2010.02.016","article-title":"Common variants of large effect in F12, KNG1, and HRG are associated with activated partial thromboplastin time","volume":"86","author":"Houlihan","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1111\/j.1538-7836.2009.03544.x","article-title":"Genetic variants associated with deep vein thrombosis: The F11 locus","volume":"7","author":"Li","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.1182\/blood-2010-11-319053","article-title":"KNG1 Ile581Thr and susceptibility to venous thrombosis","volume":"117","author":"Morange","year":"2011","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1111\/j.1538-7836.2007.02770.x","article-title":"The plasma kallikrein-kinin system: Its evolution from contact activation","volume":"5","author":"Schmaier","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2174\/1389450054546060","article-title":"Factor XII, kininogen and plasma prekallikrein in abnormal pregnancies","volume":"6","author":"Sugi","year":"2005","journal-title":"Curr. Drug Targets"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/aje\/kwq349","article-title":"The factor XII -4C>T variant and risk of common thrombotic disorders: A HuGE review and meta-analysis of evidence from observational studies","volume":"173","author":"Johnson","year":"2011","journal-title":"Am. J. Epidemiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wei, L.K., Griffiths, L.R., Kooi, C.W., and Irene, L. (2019). Meta-Analysis of Factor V, Factor VII, Factor XII, and Factor XIII-A Gene Polymorphisms and Ischemic Stroke. Medicina, 55.","DOI":"10.3390\/medicina55040101"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1038\/s41598-019-40172-x","article-title":"Minor allele of the factor V K858R variant protects from venous thrombosis only in non-carriers of factor V Leiden mutation","volume":"9","author":"Suchon","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1034\/j.1399-0004.1999.550113.x","article-title":"Mutation in the factor V gene associated with inferior vena cava thrombosis in newborns","volume":"55","author":"Gorbe","year":"1999","journal-title":"Clin. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0049-3848(00)00283-8","article-title":"Frequency of polymorphisms in the B-domain of factor V gene in APC-resistant patients","volume":"99","author":"Kostka","year":"2000","journal-title":"Thromb. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.jvs.2006.05.011","article-title":"Influence of gene polymorphisms in ulcer healing process after superficial venous surgery","volume":"44","author":"Gemmati","year":"2006","journal-title":"J. Vasc. Surg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.jvs.2006.06.006","article-title":"Prognostic role of factor XIII gene variants in nonhealing venous leg ulcers","volume":"44","author":"Tognazzo","year":"2006","journal-title":"J. Vasc. Surg."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ansani, L., Marchesini, J., Pestelli, G., Luisi, G.A., Scillitani, G., Longo, G., Milani, D., Serino, M.L., Tisato, V., and Gemmati, D. (2018). F13A1 Gene Variant (V34L) and Residual Circulating FXIIIA Levels Predict Short- and Long-Term Mortality in Acute Myocardial Infarction after Coronary Angioplasty. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092766"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1160\/TH14-11-0952","article-title":"Factor XIII-A dynamics in acute myocardial infarction: A novel prognostic biomarker?","volume":"114","author":"Gemmati","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1093\/humrep\/des289","article-title":"Soluble TRAIL is elevated in recurrent miscarriage and inhibits the in vitro adhesion and migration of HTR8 trophoblastic cells","volume":"27","author":"Agostinis","year":"2012","journal-title":"Hum. Reprod."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/6\/934\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:18:41Z","timestamp":1760163521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/6\/934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,18]]},"references-count":66,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["genes12060934"],"URL":"https:\/\/doi.org\/10.3390\/genes12060934","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,18]]}}}