{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:50:39Z","timestamp":1788306639825,"version":"build-2803163510"},"reference-count":47,"publisher":"Georg Thieme Verlag KG","issue":"08","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:C&lt;50%. One hundred twenty-three probands were genotyped for F7 mutations and three polymorphic variants and classified according to recently published clinical scores. Forty out of 123 patients (33?%) were symptomatic (43 bleedings). A severe bleeding tendency was observed only in patients with FVII:C&lt;0.10%. Epistaxis (11%) and menorrhagia (32% of females in fertile age) were the most frequent bleedings. Molecular analysis detected 48 mutations, 20 not reported in the F7 international databases. Most mutations (62%) were missense, large deletions were 6.2%. Compound heterozygotes\/homozygotes for mutations presented lower FVII:C levels compared to the other classes (Chi2=43.709, p&lt;0,001). The polymorphisms distribution was significantly different among the three F7 genotypic groups (Chi2=72.289, p&lt;0,001). The presence of truncating mutations was associated with lowest FVII:C levels (Chi2=21.351, p=0.002). This study confirms the clinical and molecular variability of the disease and the type of symptoms. It shows a good correlation between the type of F7 mutation and\/or polymorphisms and FVII:C levels, without a direct link between FVII:C and bleeding tendency. The results suggest that large deletions are underestimated and that they represent a common mechanism of F7 gene inactivation which should always be investigated in the diagnostic testing for FVII deficiency.<\/jats:p>","DOI":"10.1160\/th17-02-0085","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T03:27:24Z","timestamp":1493263644000},"page":"1455-1464","source":"Crossref","is-referenced-by-count":25,"title":["F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency"],"prefix":"10.1160","volume":"117","author":[{"given":"Gabriele","family":"Quintavalle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Riccardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna","family":"Rivolta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Martorana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Di Perna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Percesepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Tagliaferri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Ad-Hoc Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2017,11,22]]},"reference":[{"key":"10.1160\/TH17-02-0085-1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03545.x"},{"key":"10.1160\/TH17-02-0085-2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.8.2412"},{"key":"10.1160\/TH17-02-0085-3","doi-asserted-by":"crossref","unstructured":"Mariani G, Dolce A. Congenital factor VII deficiency. In: Textbook of Hemophilia. 2nd ed. Wiley-Blackwell 2010; pp. 341-347","DOI":"10.1002\/9781444318555.ch51"},{"key":"10.1160\/TH17-02-0085-4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0595"},{"key":"10.1160\/TH17-02-0085-5","unstructured":"Morrissey J. Tissue Factor and factor VII initiation of coagulation. In: Haemostasis and Thrombosis. Basic principles and Clinical Practice. 4th ed. Lippincot Williams & Wilkins 2001; pp. 89-96"},{"key":"10.1160\/TH17-02-0085-6","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1160\/TH04-10-0650","volume":"93","author":"Mariani","year":"2005","journal-title":"Thromb Haemost"},{"key":"10.1160\/TH17-02-0085-7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01844.x"},{"key":"10.1160\/TH17-02-0085-8","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20210"},{"key":"10.1160\/TH17-02-0085-9","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(2001)17:1<3::AID-HUMU2>3.0.CO;2-V"},{"key":"10.1160\/TH17-02-0085-10","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1182\/blood.V66.6.1284.1284","volume":"66","author":"Triplett","year":"1985","journal-title":"Blood"},{"key":"10.1160\/TH17-02-0085-11","first-page":"704","volume":"89","author":"Giansily-Blaizot","year":"2004","journal-title":"Haematologica"},{"key":"10.1160\/TH17-02-0085-12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2012.04653.x"},{"key":"10.1160\/TH17-02-0085-13","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1160\/TH05-06-0407","volume":"94","author":"Giansily-Blaizot","year":"2005","journal-title":"Thromb Haemost"},{"key":"10.1160\/TH17-02-0085-14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2012.04844.x"},{"key":"10.1160\/TH17-02-0085-15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01623.x"},{"key":"10.1160\/TH17-02-0085-16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02228.x"},{"key":"10.1160\/TH17-02-0085-17","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.109744"},{"key":"10.1160\/TH17-02-0085-18","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22981"},{"key":"10.1160\/TH17-02-0085-19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnf056"},{"key":"10.1160\/TH17-02-0085-20","unstructured":"The European Association for Haemophilia and Allied Disorders (EAHAD) Coagulation Factors Variant Database for Factor VII. Available at: http:\/\/www.factorvii.org. Accessed March 7, 2017"},{"key":"10.1160\/TH17-02-0085-21","doi-asserted-by":"crossref","unstructured":"Aken BL, Ayling S, Barrell D et al. The Ensembl gene annotation system. Database (Oxford) 2016; 2016 baw093. Available at: http:\/\/www.ensembl.org. Accessed March 7, 2017","DOI":"10.1093\/database\/baw093"},{"key":"10.1160\/TH17-02-0085-22","doi-asserted-by":"crossref","unstructured":"Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010 7(4): 248-249 Available at: http:\/\/genetics.harvard.edu\/pph2\/. Accessed September 5, 2016","DOI":"10.1038\/nmeth0410-248"},{"key":"10.1160\/TH17-02-0085-23","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2006.12.031"},{"key":"10.1160\/TH17-02-0085-24","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.11.2825"},{"key":"10.1160\/TH17-02-0085-25","doi-asserted-by":"publisher","DOI":"10.1126\/science.1261877"},{"key":"10.1160\/TH17-02-0085-26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-04-1199"},{"key":"10.1160\/TH17-02-0085-27","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12645"},{"key":"10.1160\/TH17-02-0085-28","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12186"},{"key":"10.1160\/TH17-02-0085-29","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000373"},{"key":"10.1160\/TH17-02-0085-30","doi-asserted-by":"publisher","DOI":"10.1186\/1746-1596-7-92"},{"key":"10.1160\/TH17-02-0085-31","doi-asserted-by":"publisher","DOI":"10.1177\/1076029611435091"},{"key":"10.1160\/TH17-02-0085-32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00921.x"},{"key":"10.1160\/TH17-02-0085-33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2009.09.007"},{"key":"10.1160\/TH17-02-0085-34","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0000000000000279"},{"key":"10.1160\/TH17-02-0085-35","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12978"},{"key":"10.1160\/TH17-02-0085-36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01910.x"},{"key":"10.1160\/TH17-02-0085-37","doi-asserted-by":"publisher","DOI":"10.1160\/TH12-10-0740"},{"key":"10.1160\/TH17-02-0085-38","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1161\/ATVB.16v01.0072","volume":"16","author":"Bernardi","year":"1996","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1160\/TH17-02-0085-39","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1225762"},{"key":"10.1160\/TH17-02-0085-40","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12604"},{"issue":"Suppl 1","key":"10.1160\/TH17-02-0085-41","doi-asserted-by":"crossref","first-page":"S36","DOI":"10.1055\/s-0037-1619821","volume":"35","author":"Rath","year":"2015","journal-title":"Hamostaseologie"},{"key":"10.1160\/TH17-02-0085-42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04408.x"},{"key":"10.1160\/TH17-02-0085-43","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12339"},{"key":"10.1160\/TH17-02-0085-44","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1998.440689.x"},{"key":"10.1160\/TH17-02-0085-45","doi-asserted-by":"publisher","DOI":"10.1159\/000071640"},{"key":"10.1160\/TH17-02-0085-46","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12160"},{"key":"10.1160\/TH17-02-0085-47","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12256"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH17-02-0085.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T06:44:06Z","timestamp":1601966646000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH17-02-0085"}},"subtitle":["Results from a genotype-phenotype study"],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":47,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2017,11,22]]},"published-print":{"date-parts":[[2017,8]]}},"URL":"https:\/\/doi.org\/10.1160\/th17-02-0085","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}