Variants p.Pro2063Ser and p.Arg324 co‐segregate in type 3 von Willebrand disease patients from Southern Brazil
Introduction von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays an important role in haemostasis. von Willebrand disease (VWD) is an inherited heterogeneous bleeding disorder caused by either a quantitative or qualitative defect of VWF. Type 3 VWD, the most severe form of the...
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| Veröffentlicht in: | Haemophilia : the official journal of the World Federation of Hemophilia 2021-03, Vol.27 (2), p.e204-e213 |
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| container_title | Haemophilia : the official journal of the World Federation of Hemophilia |
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| creator | Ornaghi, Ana Paula Meireles, Mariana Rost Botton, Mariana Rodrigues Salzano, Francisco Mauro Bandinelli, Eliane Matte, Ursula |
| description | Introduction
von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays an important role in haemostasis. von Willebrand disease (VWD) is an inherited heterogeneous bleeding disorder caused by either a quantitative or qualitative defect of VWF. Type 3 VWD, the most severe form of the disease, leads to complete quantitative VWF deficiency.
Aim
The present study aims to investigate the molecular pathogenesis of type 3 VWD patients from Southern Brazil.
Methods
The VWF gene was sequenced in 26 cases clinically diagnosed with type 3 VWD by next‐generation sequencing using Ion Torrent PGM.
Results
In 25 patients, we were able to identify both disease‐causing variants. We identified 72 different variants: 31 intronic and 41 exonic. Five novel variants were found: c.6976+5G>T; c.6885_6886insC; c.3378C>T (p.Cys1126); c.3346_3347insCCA; and c.2503G>T (p.Glu835*). Variants p.Pro2063Ser and p.Arg324* co‐segregated in 17 patients, 15 of them in homozygosity.
Conclusion
Our results may contribute to the discussion on whether the variant p.Pro2063Ser is pathogenic or not. Finally, the presence of a common haplotype in patients bearing these two variants suggests a founder effect for this variant in our region. |
| doi_str_mv | 10.1111/hae.14254 |
| format | Article |
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von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays an important role in haemostasis. von Willebrand disease (VWD) is an inherited heterogeneous bleeding disorder caused by either a quantitative or qualitative defect of VWF. Type 3 VWD, the most severe form of the disease, leads to complete quantitative VWF deficiency.
Aim
The present study aims to investigate the molecular pathogenesis of type 3 VWD patients from Southern Brazil.
Methods
The VWF gene was sequenced in 26 cases clinically diagnosed with type 3 VWD by next‐generation sequencing using Ion Torrent PGM.
Results
In 25 patients, we were able to identify both disease‐causing variants. We identified 72 different variants: 31 intronic and 41 exonic. Five novel variants were found: c.6976+5G>T; c.6885_6886insC; c.3378C>T (p.Cys1126); c.3346_3347insCCA; and c.2503G>T (p.Glu835*). Variants p.Pro2063Ser and p.Arg324* co‐segregated in 17 patients, 15 of them in homozygosity.
Conclusion
Our results may contribute to the discussion on whether the variant p.Pro2063Ser is pathogenic or not. Finally, the presence of a common haplotype in patients bearing these two variants suggests a founder effect for this variant in our region.</description><identifier>ISSN: 1351-8216</identifier><identifier>EISSN: 1365-2516</identifier><identifier>DOI: 10.1111/hae.14254</identifier><identifier>PMID: 33550700</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Amino Acid Substitution ; blood coagulation ; Brazil ; co‐segregation ; Founder effect ; gene mutations ; Haplotypes ; Hemostasis ; Humans ; type 3 von Willebrand disease ; von Willebrand Disease, Type 3 - genetics ; von Willebrand Diseases - genetics ; Von Willebrand factor ; von Willebrand Factor - genetics ; VWF gene</subject><ispartof>Haemophilia : the official journal of the World Federation of Hemophilia, 2021-03, Vol.27 (2), p.e204-e213</ispartof><rights>2021 John Wiley & Sons Ltd</rights><rights>2021 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2684-675e9a98bd6268118f67323ebba19ce9e5200ee7d0dedaf1b225022632949c6a3</citedby><cites>FETCH-LOGICAL-c2684-675e9a98bd6268118f67323ebba19ce9e5200ee7d0dedaf1b225022632949c6a3</cites><orcidid>0000-0002-4753-3184 ; 0000-0002-4022-6309</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhae.14254$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhae.14254$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33550700$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ornaghi, Ana Paula</creatorcontrib><creatorcontrib>Meireles, Mariana Rost</creatorcontrib><creatorcontrib>Botton, Mariana Rodrigues</creatorcontrib><creatorcontrib>Salzano, Francisco Mauro</creatorcontrib><creatorcontrib>Bandinelli, Eliane</creatorcontrib><creatorcontrib>Matte, Ursula</creatorcontrib><title>Variants p.Pro2063Ser and p.Arg324 co‐segregate in type 3 von Willebrand disease patients from Southern Brazil</title><title>Haemophilia : the official journal of the World Federation of Hemophilia</title><addtitle>Haemophilia</addtitle><description>Introduction
von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays an important role in haemostasis. von Willebrand disease (VWD) is an inherited heterogeneous bleeding disorder caused by either a quantitative or qualitative defect of VWF. Type 3 VWD, the most severe form of the disease, leads to complete quantitative VWF deficiency.
Aim
The present study aims to investigate the molecular pathogenesis of type 3 VWD patients from Southern Brazil.
Methods
The VWF gene was sequenced in 26 cases clinically diagnosed with type 3 VWD by next‐generation sequencing using Ion Torrent PGM.
Results
In 25 patients, we were able to identify both disease‐causing variants. We identified 72 different variants: 31 intronic and 41 exonic. Five novel variants were found: c.6976+5G>T; c.6885_6886insC; c.3378C>T (p.Cys1126); c.3346_3347insCCA; and c.2503G>T (p.Glu835*). Variants p.Pro2063Ser and p.Arg324* co‐segregated in 17 patients, 15 of them in homozygosity.
Conclusion
Our results may contribute to the discussion on whether the variant p.Pro2063Ser is pathogenic or not. Finally, the presence of a common haplotype in patients bearing these two variants suggests a founder effect for this variant in our region.</description><subject>Amino Acid Substitution</subject><subject>blood coagulation</subject><subject>Brazil</subject><subject>co‐segregation</subject><subject>Founder effect</subject><subject>gene mutations</subject><subject>Haplotypes</subject><subject>Hemostasis</subject><subject>Humans</subject><subject>type 3 von Willebrand disease</subject><subject>von Willebrand Disease, Type 3 - genetics</subject><subject>von Willebrand Diseases - genetics</subject><subject>Von Willebrand factor</subject><subject>von Willebrand Factor - genetics</subject><subject>VWF gene</subject><issn>1351-8216</issn><issn>1365-2516</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKxDAUhoMoXkYXvoAE3OiiYy5N2i7HwRsMKHhbhrQ9HSOdpiatMq58BJ_RJzHjqAvBbJKcfPk4nB-hXUqGNKyjBw1DGjMRr6BNyqWImKBydXEWNEoZlRtoy_tHQihnRK6jDc6FIAkhm6i9087opvO4HV45G575NTismzIURm7KWYwL-_H27mHqYKo7wKbB3bwFzPGzbfC9qWvI3eJDaTxoD7jVnYGFsnJ2hq9t3z2Aa_Cx06-m3kZrla497HzvA3R7enIzPo8ml2cX49EkKphM40gmAjKdpXkpw53StJIJZxzyXNOsgAwEIwQgKUkJpa5ozpggjEnOsjgrpOYDdLD0ts4-9eA7NTO-gLrWDdjeKxanScyFTLOA7v9BH23vmtCdCtKMhRnEJFCHS6pw1nsHlWqdmWk3V5SoRQwqxKC-Ygjs3rexz2dQ_pI_cw_A0RJ4MTXM_zep89HJUvkJyXqPvw</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Ornaghi, Ana Paula</creator><creator>Meireles, Mariana Rost</creator><creator>Botton, Mariana Rodrigues</creator><creator>Salzano, Francisco Mauro</creator><creator>Bandinelli, Eliane</creator><creator>Matte, Ursula</creator><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4753-3184</orcidid><orcidid>https://orcid.org/0000-0002-4022-6309</orcidid></search><sort><creationdate>202103</creationdate><title>Variants p.Pro2063Ser and p.Arg324 co‐segregate in type 3 von Willebrand disease patients from Southern Brazil</title><author>Ornaghi, Ana Paula ; Meireles, Mariana Rost ; Botton, Mariana Rodrigues ; Salzano, Francisco Mauro ; Bandinelli, Eliane ; Matte, Ursula</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2684-675e9a98bd6268118f67323ebba19ce9e5200ee7d0dedaf1b225022632949c6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Amino Acid Substitution</topic><topic>blood coagulation</topic><topic>Brazil</topic><topic>co‐segregation</topic><topic>Founder effect</topic><topic>gene mutations</topic><topic>Haplotypes</topic><topic>Hemostasis</topic><topic>Humans</topic><topic>type 3 von Willebrand disease</topic><topic>von Willebrand Disease, Type 3 - genetics</topic><topic>von Willebrand Diseases - genetics</topic><topic>Von Willebrand factor</topic><topic>von Willebrand Factor - genetics</topic><topic>VWF gene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ornaghi, Ana Paula</creatorcontrib><creatorcontrib>Meireles, Mariana Rost</creatorcontrib><creatorcontrib>Botton, Mariana Rodrigues</creatorcontrib><creatorcontrib>Salzano, Francisco Mauro</creatorcontrib><creatorcontrib>Bandinelli, Eliane</creatorcontrib><creatorcontrib>Matte, Ursula</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Haemophilia : the official journal of the World Federation of Hemophilia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ornaghi, Ana Paula</au><au>Meireles, Mariana Rost</au><au>Botton, Mariana Rodrigues</au><au>Salzano, Francisco Mauro</au><au>Bandinelli, Eliane</au><au>Matte, Ursula</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variants p.Pro2063Ser and p.Arg324 co‐segregate in type 3 von Willebrand disease patients from Southern Brazil</atitle><jtitle>Haemophilia : the official journal of the World Federation of Hemophilia</jtitle><addtitle>Haemophilia</addtitle><date>2021-03</date><risdate>2021</risdate><volume>27</volume><issue>2</issue><spage>e204</spage><epage>e213</epage><pages>e204-e213</pages><issn>1351-8216</issn><eissn>1365-2516</eissn><abstract>Introduction
von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays an important role in haemostasis. von Willebrand disease (VWD) is an inherited heterogeneous bleeding disorder caused by either a quantitative or qualitative defect of VWF. Type 3 VWD, the most severe form of the disease, leads to complete quantitative VWF deficiency.
Aim
The present study aims to investigate the molecular pathogenesis of type 3 VWD patients from Southern Brazil.
Methods
The VWF gene was sequenced in 26 cases clinically diagnosed with type 3 VWD by next‐generation sequencing using Ion Torrent PGM.
Results
In 25 patients, we were able to identify both disease‐causing variants. We identified 72 different variants: 31 intronic and 41 exonic. Five novel variants were found: c.6976+5G>T; c.6885_6886insC; c.3378C>T (p.Cys1126); c.3346_3347insCCA; and c.2503G>T (p.Glu835*). Variants p.Pro2063Ser and p.Arg324* co‐segregated in 17 patients, 15 of them in homozygosity.
Conclusion
Our results may contribute to the discussion on whether the variant p.Pro2063Ser is pathogenic or not. Finally, the presence of a common haplotype in patients bearing these two variants suggests a founder effect for this variant in our region.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33550700</pmid><doi>10.1111/hae.14254</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-4753-3184</orcidid><orcidid>https://orcid.org/0000-0002-4022-6309</orcidid></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Amino Acid Substitution blood coagulation Brazil co‐segregation Founder effect gene mutations Haplotypes Hemostasis Humans type 3 von Willebrand disease von Willebrand Disease, Type 3 - genetics von Willebrand Diseases - genetics Von Willebrand factor von Willebrand Factor - genetics VWF gene |
| title | Variants p.Pro2063Ser and p.Arg324 co‐segregate in type 3 von Willebrand disease patients from Southern Brazil |
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