Exome Sequencing and Clot Lysis Experiments Demonstrate the R458C Mutation of the Alpha Chain of Fibrinogen to be Associated with Impaired Fibrinolysis in a Family with Thrombophilia
Aim: We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques. Methods: Exome sequencing was performed in three familial cases with venous thromboembolic disease and one fa...
Gespeichert in:
Veröffentlicht in: | Journal of Atherosclerosis and Thrombosis 2016/04/01, Vol.23(4), pp.431-440 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 440 |
---|---|
container_issue | 4 |
container_start_page | 431 |
container_title | Journal of Atherosclerosis and Thrombosis |
container_volume | 23 |
creator | Fernández-Cadenas, Israel Penalba, Anna Boada, Cristina MsC, Caty Carrerra Bueno, Santiago Rodriguez Quiroga, Adoración Monasterio, Jasone Delgado, Pilar Anglés-Cano, Eduardo Montaner, Joan |
description | Aim: We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques. Methods: Exome sequencing was performed in three familial cases with venous thromboembolic disease and one familial control using NimbleGen exome array. Clot lysis experiments were performed to analyze the reasons of the altered fibrinolytic activity caused by the mutation found. Results: We found a mutation that consists of a R458C substitution on the fibrinogen alpha chain (FGA) gene confirmed in 13 new familial subjects that causes a rare subtype of dysfibrinogenemia characterized by venous thromboembolic events. The mutation was already reported to be associated with a fibrinogen variant called fibrinogen Bordeaux. Clot-lysis experiments showed a decreased and slower fibrinolytic activity in carriers of this mutation as compared to normal subjects, thus demonstrating an impaired fibrinolysis of fibrinogen Bordeaux. Conclusions: The exome sequencing and clot-lysis experiments might be powerful tools to diagnose idiopathic thrombophilias after an unsuccessful set of biochemical laboratory tests. Fibrinogen Bordeaux is associated with impaired fibrinolysis in this family with idiopathic thrombophilia. |
doi_str_mv | 10.5551/jat.30676 |
format | Article |
fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_inserm_01305109v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1778708205</sourcerecordid><originalsourceid>FETCH-LOGICAL-c503t-b552e51efba7cb0856269074638bd8cf39243593f65c1fdf1b0182a99514c60e3</originalsourceid><addsrcrecordid>eNo9kVFv0zAQxyMEYmPwwBdAfmQSHXYcJ84Tqkq7TSpCgvFsOc6lceXYwXZh_WJ8vnlJ6Yt9vvv5f7r7Z9l7gm8YY-TzXsYbisuqfJFdEs7xgvKKvkwxLVJcVPwiexPCHmNKGctfZxd5yTghnF5m_9aPbgD0E34fwCptd0jaFq2Mi2h7DDqg9eMIXg9gY0BfYXA2RC8joNgD-lEwvkLfDlFG7Sxy3ZRdmrGXaNVLPaU2uvHauh1YFB1qUj0Ep3TSaNFfHXt0P4xS-_Q6kWbqmz5LtJGDNscZe-i9Gxo39tpo-TZ71UkT4N3pvsp-bdYPq7vF9vvt_Wq5XSiGaVw0aVxgBLpGVqrBnJV5WeOqKClvWq46WucFZTXtSqZI13akwYTnsq4ZKVSJgV5ln2bdXhoxpj1IfxROanG33AptA_hBYEIxI7j-QxL-ccZH79JCQxSDDgqMkRbcIQhSVbzCPMcsodczqrwLwUN3lidYPLsqkqticjWxH06yh2aA9kz-tzEBX2ZgH6LcwRmQPmplYJLKqSiej0nyXFG99AIsfQJdTbUa</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1778708205</pqid></control><display><type>article</type><title>Exome Sequencing and Clot Lysis Experiments Demonstrate the R458C Mutation of the Alpha Chain of Fibrinogen to be Associated with Impaired Fibrinolysis in a Family with Thrombophilia</title><source>Open Access: PubMed Central</source><source>MEDLINE</source><source>J-STAGE</source><source>Free E-Journal (出版社公開部分のみ)</source><creator>Fernández-Cadenas, Israel ; Penalba, Anna ; Boada, Cristina ; MsC, Caty Carrerra ; Bueno, Santiago Rodriguez ; Quiroga, Adoración ; Monasterio, Jasone ; Delgado, Pilar ; Anglés-Cano, Eduardo ; Montaner, Joan</creator><creatorcontrib>Fernández-Cadenas, Israel ; Penalba, Anna ; Boada, Cristina ; MsC, Caty Carrerra ; Bueno, Santiago Rodriguez ; Quiroga, Adoración ; Monasterio, Jasone ; Delgado, Pilar ; Anglés-Cano, Eduardo ; Montaner, Joan</creatorcontrib><description>Aim: We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques. Methods: Exome sequencing was performed in three familial cases with venous thromboembolic disease and one familial control using NimbleGen exome array. Clot lysis experiments were performed to analyze the reasons of the altered fibrinolytic activity caused by the mutation found. Results: We found a mutation that consists of a R458C substitution on the fibrinogen alpha chain (FGA) gene confirmed in 13 new familial subjects that causes a rare subtype of dysfibrinogenemia characterized by venous thromboembolic events. The mutation was already reported to be associated with a fibrinogen variant called fibrinogen Bordeaux. Clot-lysis experiments showed a decreased and slower fibrinolytic activity in carriers of this mutation as compared to normal subjects, thus demonstrating an impaired fibrinolysis of fibrinogen Bordeaux. Conclusions: The exome sequencing and clot-lysis experiments might be powerful tools to diagnose idiopathic thrombophilias after an unsuccessful set of biochemical laboratory tests. Fibrinogen Bordeaux is associated with impaired fibrinolysis in this family with idiopathic thrombophilia.</description><identifier>ISSN: 1340-3478</identifier><identifier>EISSN: 1880-3873</identifier><identifier>DOI: 10.5551/jat.30676</identifier><identifier>PMID: 26581183</identifier><language>eng</language><publisher>Japan: Japan Atherosclerosis Society</publisher><subject>Biochemistry, Molecular Biology ; Blood Coagulation ; Blood Coagulation Tests ; Coagulation ; Dysfibrinogenemia ; Exome ; Family Health ; Female ; Fibrin - genetics ; Fibrinogen ; Fibrinogen - genetics ; Genetics ; Hematology ; Human health and pathology ; Humans ; Life Sciences ; Male ; Mutation ; Pedigree ; Sequence Analysis, DNA ; Thrombin - genetics ; Thrombophilia - genetics ; Thrombosis ; Thrombosis - genetics ; Venous Thromboembolism - genetics</subject><ispartof>Journal of Atherosclerosis and Thrombosis, 2016/04/01, Vol.23(4), pp.431-440</ispartof><rights>2016 Japan Atherosclerosis Society</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-b552e51efba7cb0856269074638bd8cf39243593f65c1fdf1b0182a99514c60e3</citedby><cites>FETCH-LOGICAL-c503t-b552e51efba7cb0856269074638bd8cf39243593f65c1fdf1b0182a99514c60e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1883,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26581183$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-01305109$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernández-Cadenas, Israel</creatorcontrib><creatorcontrib>Penalba, Anna</creatorcontrib><creatorcontrib>Boada, Cristina</creatorcontrib><creatorcontrib>MsC, Caty Carrerra</creatorcontrib><creatorcontrib>Bueno, Santiago Rodriguez</creatorcontrib><creatorcontrib>Quiroga, Adoración</creatorcontrib><creatorcontrib>Monasterio, Jasone</creatorcontrib><creatorcontrib>Delgado, Pilar</creatorcontrib><creatorcontrib>Anglés-Cano, Eduardo</creatorcontrib><creatorcontrib>Montaner, Joan</creatorcontrib><title>Exome Sequencing and Clot Lysis Experiments Demonstrate the R458C Mutation of the Alpha Chain of Fibrinogen to be Associated with Impaired Fibrinolysis in a Family with Thrombophilia</title><title>Journal of Atherosclerosis and Thrombosis</title><addtitle>JAT</addtitle><description>Aim: We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques. Methods: Exome sequencing was performed in three familial cases with venous thromboembolic disease and one familial control using NimbleGen exome array. Clot lysis experiments were performed to analyze the reasons of the altered fibrinolytic activity caused by the mutation found. Results: We found a mutation that consists of a R458C substitution on the fibrinogen alpha chain (FGA) gene confirmed in 13 new familial subjects that causes a rare subtype of dysfibrinogenemia characterized by venous thromboembolic events. The mutation was already reported to be associated with a fibrinogen variant called fibrinogen Bordeaux. Clot-lysis experiments showed a decreased and slower fibrinolytic activity in carriers of this mutation as compared to normal subjects, thus demonstrating an impaired fibrinolysis of fibrinogen Bordeaux. Conclusions: The exome sequencing and clot-lysis experiments might be powerful tools to diagnose idiopathic thrombophilias after an unsuccessful set of biochemical laboratory tests. Fibrinogen Bordeaux is associated with impaired fibrinolysis in this family with idiopathic thrombophilia.</description><subject>Biochemistry, Molecular Biology</subject><subject>Blood Coagulation</subject><subject>Blood Coagulation Tests</subject><subject>Coagulation</subject><subject>Dysfibrinogenemia</subject><subject>Exome</subject><subject>Family Health</subject><subject>Female</subject><subject>Fibrin - genetics</subject><subject>Fibrinogen</subject><subject>Fibrinogen - genetics</subject><subject>Genetics</subject><subject>Hematology</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mutation</subject><subject>Pedigree</subject><subject>Sequence Analysis, DNA</subject><subject>Thrombin - genetics</subject><subject>Thrombophilia - genetics</subject><subject>Thrombosis</subject><subject>Thrombosis - genetics</subject><subject>Venous Thromboembolism - genetics</subject><issn>1340-3478</issn><issn>1880-3873</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kVFv0zAQxyMEYmPwwBdAfmQSHXYcJ84Tqkq7TSpCgvFsOc6lceXYwXZh_WJ8vnlJ6Yt9vvv5f7r7Z9l7gm8YY-TzXsYbisuqfJFdEs7xgvKKvkwxLVJcVPwiexPCHmNKGctfZxd5yTghnF5m_9aPbgD0E34fwCptd0jaFq2Mi2h7DDqg9eMIXg9gY0BfYXA2RC8joNgD-lEwvkLfDlFG7Sxy3ZRdmrGXaNVLPaU2uvHauh1YFB1qUj0Ep3TSaNFfHXt0P4xS-_Q6kWbqmz5LtJGDNscZe-i9Gxo39tpo-TZ71UkT4N3pvsp-bdYPq7vF9vvt_Wq5XSiGaVw0aVxgBLpGVqrBnJV5WeOqKClvWq46WucFZTXtSqZI13akwYTnsq4ZKVSJgV5ln2bdXhoxpj1IfxROanG33AptA_hBYEIxI7j-QxL-ccZH79JCQxSDDgqMkRbcIQhSVbzCPMcsodczqrwLwUN3lidYPLsqkqticjWxH06yh2aA9kz-tzEBX2ZgH6LcwRmQPmplYJLKqSiej0nyXFG99AIsfQJdTbUa</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Fernández-Cadenas, Israel</creator><creator>Penalba, Anna</creator><creator>Boada, Cristina</creator><creator>MsC, Caty Carrerra</creator><creator>Bueno, Santiago Rodriguez</creator><creator>Quiroga, Adoración</creator><creator>Monasterio, Jasone</creator><creator>Delgado, Pilar</creator><creator>Anglés-Cano, Eduardo</creator><creator>Montaner, Joan</creator><general>Japan Atherosclerosis Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope></search><sort><creationdate>20160101</creationdate><title>Exome Sequencing and Clot Lysis Experiments Demonstrate the R458C Mutation of the Alpha Chain of Fibrinogen to be Associated with Impaired Fibrinolysis in a Family with Thrombophilia</title><author>Fernández-Cadenas, Israel ; Penalba, Anna ; Boada, Cristina ; MsC, Caty Carrerra ; Bueno, Santiago Rodriguez ; Quiroga, Adoración ; Monasterio, Jasone ; Delgado, Pilar ; Anglés-Cano, Eduardo ; Montaner, Joan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-b552e51efba7cb0856269074638bd8cf39243593f65c1fdf1b0182a99514c60e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Biochemistry, Molecular Biology</topic><topic>Blood Coagulation</topic><topic>Blood Coagulation Tests</topic><topic>Coagulation</topic><topic>Dysfibrinogenemia</topic><topic>Exome</topic><topic>Family Health</topic><topic>Female</topic><topic>Fibrin - genetics</topic><topic>Fibrinogen</topic><topic>Fibrinogen - genetics</topic><topic>Genetics</topic><topic>Hematology</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Mutation</topic><topic>Pedigree</topic><topic>Sequence Analysis, DNA</topic><topic>Thrombin - genetics</topic><topic>Thrombophilia - genetics</topic><topic>Thrombosis</topic><topic>Thrombosis - genetics</topic><topic>Venous Thromboembolism - genetics</topic><toplevel>online_resources</toplevel><creatorcontrib>Fernández-Cadenas, Israel</creatorcontrib><creatorcontrib>Penalba, Anna</creatorcontrib><creatorcontrib>Boada, Cristina</creatorcontrib><creatorcontrib>MsC, Caty Carrerra</creatorcontrib><creatorcontrib>Bueno, Santiago Rodriguez</creatorcontrib><creatorcontrib>Quiroga, Adoración</creatorcontrib><creatorcontrib>Monasterio, Jasone</creatorcontrib><creatorcontrib>Delgado, Pilar</creatorcontrib><creatorcontrib>Anglés-Cano, Eduardo</creatorcontrib><creatorcontrib>Montaner, Joan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Journal of Atherosclerosis and Thrombosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernández-Cadenas, Israel</au><au>Penalba, Anna</au><au>Boada, Cristina</au><au>MsC, Caty Carrerra</au><au>Bueno, Santiago Rodriguez</au><au>Quiroga, Adoración</au><au>Monasterio, Jasone</au><au>Delgado, Pilar</au><au>Anglés-Cano, Eduardo</au><au>Montaner, Joan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exome Sequencing and Clot Lysis Experiments Demonstrate the R458C Mutation of the Alpha Chain of Fibrinogen to be Associated with Impaired Fibrinolysis in a Family with Thrombophilia</atitle><jtitle>Journal of Atherosclerosis and Thrombosis</jtitle><addtitle>JAT</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>23</volume><issue>4</issue><spage>431</spage><epage>440</epage><pages>431-440</pages><issn>1340-3478</issn><eissn>1880-3873</eissn><abstract>Aim: We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques. Methods: Exome sequencing was performed in three familial cases with venous thromboembolic disease and one familial control using NimbleGen exome array. Clot lysis experiments were performed to analyze the reasons of the altered fibrinolytic activity caused by the mutation found. Results: We found a mutation that consists of a R458C substitution on the fibrinogen alpha chain (FGA) gene confirmed in 13 new familial subjects that causes a rare subtype of dysfibrinogenemia characterized by venous thromboembolic events. The mutation was already reported to be associated with a fibrinogen variant called fibrinogen Bordeaux. Clot-lysis experiments showed a decreased and slower fibrinolytic activity in carriers of this mutation as compared to normal subjects, thus demonstrating an impaired fibrinolysis of fibrinogen Bordeaux. Conclusions: The exome sequencing and clot-lysis experiments might be powerful tools to diagnose idiopathic thrombophilias after an unsuccessful set of biochemical laboratory tests. Fibrinogen Bordeaux is associated with impaired fibrinolysis in this family with idiopathic thrombophilia.</abstract><cop>Japan</cop><pub>Japan Atherosclerosis Society</pub><pmid>26581183</pmid><doi>10.5551/jat.30676</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1340-3478 |
ispartof | Journal of Atherosclerosis and Thrombosis, 2016/04/01, Vol.23(4), pp.431-440 |
issn | 1340-3478 1880-3873 |
language | eng |
recordid | cdi_hal_primary_oai_HAL_inserm_01305109v1 |
source | Open Access: PubMed Central; MEDLINE; J-STAGE; Free E-Journal (出版社公開部分のみ) |
subjects | Biochemistry, Molecular Biology Blood Coagulation Blood Coagulation Tests Coagulation Dysfibrinogenemia Exome Family Health Female Fibrin - genetics Fibrinogen Fibrinogen - genetics Genetics Hematology Human health and pathology Humans Life Sciences Male Mutation Pedigree Sequence Analysis, DNA Thrombin - genetics Thrombophilia - genetics Thrombosis Thrombosis - genetics Venous Thromboembolism - genetics |
title | Exome Sequencing and Clot Lysis Experiments Demonstrate the R458C Mutation of the Alpha Chain of Fibrinogen to be Associated with Impaired Fibrinolysis in a Family with Thrombophilia |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T10%3A11%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Exome%20Sequencing%20and%20Clot%20Lysis%20Experiments%20Demonstrate%20the%20R458C%20Mutation%20of%20the%20Alpha%20Chain%20of%20Fibrinogen%20to%20be%20Associated%20with%20Impaired%20Fibrinolysis%20in%20a%20Family%20with%20Thrombophilia&rft.jtitle=Journal%20of%20Atherosclerosis%20and%20Thrombosis&rft.au=Fern%C3%A1ndez-Cadenas,%20Israel&rft.date=2016-01-01&rft.volume=23&rft.issue=4&rft.spage=431&rft.epage=440&rft.pages=431-440&rft.issn=1340-3478&rft.eissn=1880-3873&rft_id=info:doi/10.5551/jat.30676&rft_dat=%3Cproquest_hal_p%3E1778708205%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1778708205&rft_id=info:pmid/26581183&rfr_iscdi=true |