A novel type 2A von Willebrand factor mutation (V1499E) associated with variable clinical expression
We have identified a previously unreported mutation, V1499E, with a high penetrance in a family with type 2A von Willebrand disease. Affected family members were difficult to identify owing to variable von Willebrand factor (VWF) levels, variable expression of VWF multimers, and clinical symptoms. R...
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| Veröffentlicht in: | Journal of pediatric hematology/oncology 2009-04, Vol.31 (4), p.277-280 |
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| container_title | Journal of pediatric hematology/oncology |
| container_volume | 31 |
| creator | van den Heuvel, Esther de Laat, Bas Eckmann, Carel M Michiels, Jan J Schneppenheim, Reinhard Budde, Ulrich van Mourik, Jan A Versteegh, Florens G A |
| description | We have identified a previously unreported mutation, V1499E, with a high penetrance in a family with type 2A von Willebrand disease. Affected family members were difficult to identify owing to variable von Willebrand factor (VWF) levels, variable expression of VWF multimers, and clinical symptoms. Recombinant V1499E-VWF was more readily cleaved by ADAMTS13 than the wild-type protein, suggesting that V1499E is the causative mutation. Surprisingly, this seemingly novel unique mutation was also found in other family members in 2 other hospitals displaying the same variable laboratory and clinical symptoms. The fact that this V1499E mutation was detected independently in 3 hospitals is strongly in favor of 1 central database, especially considering the variable laboratory and clinical picture. |
| doi_str_mv | 10.1097/MPH.0b013e31819d9119 |
| format | Article |
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Affected family members were difficult to identify owing to variable von Willebrand factor (VWF) levels, variable expression of VWF multimers, and clinical symptoms. Recombinant V1499E-VWF was more readily cleaved by ADAMTS13 than the wild-type protein, suggesting that V1499E is the causative mutation. Surprisingly, this seemingly novel unique mutation was also found in other family members in 2 other hospitals displaying the same variable laboratory and clinical symptoms. The fact that this V1499E mutation was detected independently in 3 hospitals is strongly in favor of 1 central database, especially considering the variable laboratory and clinical picture.</description><identifier>ISSN: 1077-4114</identifier><identifier>EISSN: 1536-3678</identifier><identifier>DOI: 10.1097/MPH.0b013e31819d9119</identifier><identifier>PMID: 19346881</identifier><language>eng</language><publisher>United States</publisher><subject>ADAM Proteins - metabolism ; ADAM Proteins - pharmacology ; ADAMTS13 Protein ; Child ; Child, Preschool ; Databases, Genetic ; Family Health ; Female ; Genotype ; Hemorrhage - genetics ; Humans ; Infant ; Male ; Penetrance ; Phenotype ; Point Mutation ; von Willebrand Factor - genetics ; von Willebrand Factor - metabolism</subject><ispartof>Journal of pediatric hematology/oncology, 2009-04, Vol.31 (4), p.277-280</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c305t-54ba0714b4249e7f78cb8c9f98438b579a39e99ab517a4419793e22d46c48a913</citedby><cites>FETCH-LOGICAL-c305t-54ba0714b4249e7f78cb8c9f98438b579a39e99ab517a4419793e22d46c48a913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19346881$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van den Heuvel, Esther</creatorcontrib><creatorcontrib>de Laat, Bas</creatorcontrib><creatorcontrib>Eckmann, Carel M</creatorcontrib><creatorcontrib>Michiels, Jan J</creatorcontrib><creatorcontrib>Schneppenheim, Reinhard</creatorcontrib><creatorcontrib>Budde, Ulrich</creatorcontrib><creatorcontrib>van Mourik, Jan A</creatorcontrib><creatorcontrib>Versteegh, Florens G A</creatorcontrib><title>A novel type 2A von Willebrand factor mutation (V1499E) associated with variable clinical expression</title><title>Journal of pediatric hematology/oncology</title><addtitle>J Pediatr Hematol Oncol</addtitle><description>We have identified a previously unreported mutation, V1499E, with a high penetrance in a family with type 2A von Willebrand disease. Affected family members were difficult to identify owing to variable von Willebrand factor (VWF) levels, variable expression of VWF multimers, and clinical symptoms. Recombinant V1499E-VWF was more readily cleaved by ADAMTS13 than the wild-type protein, suggesting that V1499E is the causative mutation. Surprisingly, this seemingly novel unique mutation was also found in other family members in 2 other hospitals displaying the same variable laboratory and clinical symptoms. The fact that this V1499E mutation was detected independently in 3 hospitals is strongly in favor of 1 central database, especially considering the variable laboratory and clinical picture.</description><subject>ADAM Proteins - metabolism</subject><subject>ADAM Proteins - pharmacology</subject><subject>ADAMTS13 Protein</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Databases, Genetic</subject><subject>Family Health</subject><subject>Female</subject><subject>Genotype</subject><subject>Hemorrhage - genetics</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Penetrance</subject><subject>Phenotype</subject><subject>Point Mutation</subject><subject>von Willebrand Factor - genetics</subject><subject>von Willebrand Factor - metabolism</subject><issn>1077-4114</issn><issn>1536-3678</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE1L7DAUhoMo6lX_gUhW4l1Uc5q0yVkO4scFRRd-LEuSnmIk045JZ9R_b8UB4a7OC-d93sXD2CGIUxCoz27vr0-FEyBJggFsEQA32C5Usi5krc3mlIXWhQJQO-xPzq9CgJaq3GY7gFLVxsAua2e8H1YU-fi5IF7O-Gro-XOIkVyyfcs768ch8flytGOYXidPoBAv_nKb8-CDHanl72F84SubgnWRuI-hD95GTh-LRDlP1D7b6mzMdLC-e-zx8uLh_Lq4ubv6dz67KbwU1VhUylmhQTlVKiTdaeOd8dihUdK4SqOVSIjWVaCtUoAaJZVlq2qvjEWQe-z4Z3eRhrcl5bGZh-wpRtvTsMxNraEEbcxUVD9Fn4acE3XNIoW5TZ8NiObbbjPZbf63O2FH6_2lm1P7C611yi8enXVd</recordid><startdate>200904</startdate><enddate>200904</enddate><creator>van den Heuvel, Esther</creator><creator>de Laat, Bas</creator><creator>Eckmann, Carel M</creator><creator>Michiels, Jan J</creator><creator>Schneppenheim, Reinhard</creator><creator>Budde, Ulrich</creator><creator>van Mourik, Jan A</creator><creator>Versteegh, Florens G A</creator><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></search><sort><creationdate>200904</creationdate><title>A novel type 2A von Willebrand factor mutation (V1499E) associated with variable clinical expression</title><author>van den Heuvel, Esther ; de Laat, Bas ; Eckmann, Carel M ; Michiels, Jan J ; Schneppenheim, Reinhard ; Budde, Ulrich ; van Mourik, Jan A ; Versteegh, Florens G A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c305t-54ba0714b4249e7f78cb8c9f98438b579a39e99ab517a4419793e22d46c48a913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>ADAM Proteins - metabolism</topic><topic>ADAM Proteins - pharmacology</topic><topic>ADAMTS13 Protein</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Databases, Genetic</topic><topic>Family Health</topic><topic>Female</topic><topic>Genotype</topic><topic>Hemorrhage - genetics</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Penetrance</topic><topic>Phenotype</topic><topic>Point Mutation</topic><topic>von Willebrand Factor - genetics</topic><topic>von Willebrand Factor - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van den Heuvel, Esther</creatorcontrib><creatorcontrib>de Laat, Bas</creatorcontrib><creatorcontrib>Eckmann, Carel M</creatorcontrib><creatorcontrib>Michiels, Jan J</creatorcontrib><creatorcontrib>Schneppenheim, Reinhard</creatorcontrib><creatorcontrib>Budde, Ulrich</creatorcontrib><creatorcontrib>van Mourik, Jan A</creatorcontrib><creatorcontrib>Versteegh, Florens G A</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><jtitle>Journal of pediatric hematology/oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van den Heuvel, Esther</au><au>de Laat, Bas</au><au>Eckmann, Carel M</au><au>Michiels, Jan J</au><au>Schneppenheim, Reinhard</au><au>Budde, Ulrich</au><au>van Mourik, Jan A</au><au>Versteegh, Florens G A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel type 2A von Willebrand factor mutation (V1499E) associated with variable clinical expression</atitle><jtitle>Journal of pediatric hematology/oncology</jtitle><addtitle>J Pediatr Hematol Oncol</addtitle><date>2009-04</date><risdate>2009</risdate><volume>31</volume><issue>4</issue><spage>277</spage><epage>280</epage><pages>277-280</pages><issn>1077-4114</issn><eissn>1536-3678</eissn><abstract>We have identified a previously unreported mutation, V1499E, with a high penetrance in a family with type 2A von Willebrand disease. Affected family members were difficult to identify owing to variable von Willebrand factor (VWF) levels, variable expression of VWF multimers, and clinical symptoms. Recombinant V1499E-VWF was more readily cleaved by ADAMTS13 than the wild-type protein, suggesting that V1499E is the causative mutation. Surprisingly, this seemingly novel unique mutation was also found in other family members in 2 other hospitals displaying the same variable laboratory and clinical symptoms. The fact that this V1499E mutation was detected independently in 3 hospitals is strongly in favor of 1 central database, especially considering the variable laboratory and clinical picture.</abstract><cop>United States</cop><pmid>19346881</pmid><doi>10.1097/MPH.0b013e31819d9119</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1077-4114 |
| ispartof | Journal of pediatric hematology/oncology, 2009-04, Vol.31 (4), p.277-280 |
| issn | 1077-4114 1536-3678 |
| language | eng |
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| source | MEDLINE; Journals@Ovid Complete |
| subjects | ADAM Proteins - metabolism ADAM Proteins - pharmacology ADAMTS13 Protein Child Child, Preschool Databases, Genetic Family Health Female Genotype Hemorrhage - genetics Humans Infant Male Penetrance Phenotype Point Mutation von Willebrand Factor - genetics von Willebrand Factor - metabolism |
| title | A novel type 2A von Willebrand factor mutation (V1499E) associated with variable clinical expression |
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