Combined effects of two mutations in von Willebrand disease 2M phenotype

Autores
Woods, Adriana Inés; Paiva Palomino, Juvenal Hernán; Kempfer, Ana Catalina; Primrose, Debora Marina; Blanco, Alicia Noemi; Sánchez Luceros, Analía Gabriela; Lazzari, María Ángela
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Type 2M von Willebrand disease (VWD2M) is usually characterized byVWF:RCo/VWF:Ag<0.6 and normal multimeric profile; desmopressin (DDAVP) challengetest commonly shows poor response of VWF:RCo.Objective: We describe the bleeding tendency and the laboratory phenotype in a patient carrying two heterozygous mutations affecting VWF-A1 domain and VWF-A2domain.Subjects/methods: A 12-year-old patient (O blood group) with severe hemorrhagictendency was phenotypically and genotypically analyzed; his parents were alsostudied.Results: The proband showed decrease FVIII:C, VWF:RCo/VWF:Ag, and VWF:CB6/VWF:Ag ratios, but normal platelet count, VWF:CB1/VWF:Ag ratio, VWFpp and multimeric pattern, suggesting a VWD2M phenotype. The DDAVP challenge test, compared to controls (VWD2M patients with mutations in VWF-A1 domain), showed lower increase of FVIII:C and VWF:Ag than in heterozygous, but very similar to homozygous control. Two mutations were found in heterozygous and trans presentation: p.Pro1648fs*45 and a novel missense mutation, p.Arg1426Cys. The mother was p.Arg1426Cys heterozygous carrier, with few clinical symptoms. The father was asymptomatic, with no mutations. The p.Pro1648fs*45 was considered an apparent de novo mutation; proband?s AS-PCR revealed mosaicism in the paternal allele. According to the predicted models, p.Arg1426Cys would not be affecting the binding of GPIbα to A1 domain, whereas p.Pro1648fs*45 seems to modify the folding of A2 domain, and in this way, it would affect the binding to GPIbα and type VI collagen. We believe that the combination of these two heterozygous mutations, in a child with O blood group, could result in a defective phenotype enhancer.eCollection 2018 Jan
Fil: Woods, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Paiva Palomino, Juvenal Hernán. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Kempfer, Ana Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Primrose, Debora Marina. Universidad de Morón. Facultad de Agronomía y Ciencias Agroalimentarias; Argentina
Fil: Blanco, Alicia Noemi. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Sánchez Luceros, Analía Gabriela. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
desmopressin
hemorrhage
mutations
type 2M
von Willebrand disease
von Willbrand factor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/95515
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/95515
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Combined effects of two mutations in von Willebrand disease 2M phenotypeWoods, Adriana InésPaiva Palomino, Juvenal HernánKempfer, Ana CatalinaPrimrose, Debora MarinaBlanco, Alicia NoemiSánchez Luceros, Analía GabrielaLazzari, María Ángeladesmopressinhemorrhagemutationstype 2Mvon Willebrand diseasevon Willbrand factorhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: Type 2M von Willebrand disease (VWD2M) is usually characterized byVWF:RCo/VWF:Ag<0.6 and normal multimeric profile; desmopressin (DDAVP) challengetest commonly shows poor response of VWF:RCo.Objective: We describe the bleeding tendency and the laboratory phenotype in a patient carrying two heterozygous mutations affecting VWF-A1 domain and VWF-A2domain.Subjects/methods: A 12-year-old patient (O blood group) with severe hemorrhagictendency was phenotypically and genotypically analyzed; his parents were alsostudied.Results: The proband showed decrease FVIII:C, VWF:RCo/VWF:Ag, and VWF:CB6/VWF:Ag ratios, but normal platelet count, VWF:CB1/VWF:Ag ratio, VWFpp and multimeric pattern, suggesting a VWD2M phenotype. The DDAVP challenge test, compared to controls (VWD2M patients with mutations in VWF-A1 domain), showed lower increase of FVIII:C and VWF:Ag than in heterozygous, but very similar to homozygous control. Two mutations were found in heterozygous and trans presentation: p.Pro1648fs*45 and a novel missense mutation, p.Arg1426Cys. The mother was p.Arg1426Cys heterozygous carrier, with few clinical symptoms. The father was asymptomatic, with no mutations. The p.Pro1648fs*45 was considered an apparent de novo mutation; proband?s AS-PCR revealed mosaicism in the paternal allele. According to the predicted models, p.Arg1426Cys would not be affecting the binding of GPIbα to A1 domain, whereas p.Pro1648fs*45 seems to modify the folding of A2 domain, and in this way, it would affect the binding to GPIbα and type VI collagen. We believe that the combination of these two heterozygous mutations, in a child with O blood group, could result in a defective phenotype enhancer.eCollection 2018 JanFil: Woods, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Paiva Palomino, Juvenal Hernán. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; ArgentinaFil: Kempfer, Ana Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Primrose, Debora Marina. Universidad de Morón. Facultad de Agronomía y Ciencias Agroalimentarias; ArgentinaFil: Blanco, Alicia Noemi. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; ArgentinaFil: Sánchez Luceros, Analía Gabriela. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaWiley2018-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95515Woods, Adriana Inés; Paiva Palomino, Juvenal Hernán; Kempfer, Ana Catalina; Primrose, Debora Marina; Blanco, Alicia Noemi; et al.; Combined effects of two mutations in von Willebrand disease 2M phenotype; Wiley; Research and Practice in Thrombosis and Haemostasis; 2; 1; 1-2018; 162-1672475-0379CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/rth2.12067info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/rth2.12067info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:51:38Zoai:ri.conicet.gov.ar:11336/95515instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 11:51:38.934CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Combined effects of two mutations in von Willebrand disease 2M phenotype
title Combined effects of two mutations in von Willebrand disease 2M phenotype
spellingShingle Combined effects of two mutations in von Willebrand disease 2M phenotype
Woods, Adriana Inés
desmopressin
hemorrhage
mutations
type 2M
von Willebrand disease
von Willbrand factor
title_short Combined effects of two mutations in von Willebrand disease 2M phenotype
title_full Combined effects of two mutations in von Willebrand disease 2M phenotype
title_fullStr Combined effects of two mutations in von Willebrand disease 2M phenotype
title_full_unstemmed Combined effects of two mutations in von Willebrand disease 2M phenotype
title_sort Combined effects of two mutations in von Willebrand disease 2M phenotype
dc.creator.none.fl_str_mv Woods, Adriana Inés
Paiva Palomino, Juvenal Hernán
Kempfer, Ana Catalina
Primrose, Debora Marina
Blanco, Alicia Noemi
Sánchez Luceros, Analía Gabriela
Lazzari, María Ángela
author Woods, Adriana Inés
author_facet Woods, Adriana Inés
Paiva Palomino, Juvenal Hernán
Kempfer, Ana Catalina
Primrose, Debora Marina
Blanco, Alicia Noemi
Sánchez Luceros, Analía Gabriela
Lazzari, María Ángela
author_role author
author2 Paiva Palomino, Juvenal Hernán
Kempfer, Ana Catalina
Primrose, Debora Marina
Blanco, Alicia Noemi
Sánchez Luceros, Analía Gabriela
Lazzari, María Ángela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv desmopressin
hemorrhage
mutations
type 2M
von Willebrand disease
von Willbrand factor
topic desmopressin
hemorrhage
mutations
type 2M
von Willebrand disease
von Willbrand factor
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Type 2M von Willebrand disease (VWD2M) is usually characterized byVWF:RCo/VWF:Ag<0.6 and normal multimeric profile; desmopressin (DDAVP) challengetest commonly shows poor response of VWF:RCo.Objective: We describe the bleeding tendency and the laboratory phenotype in a patient carrying two heterozygous mutations affecting VWF-A1 domain and VWF-A2domain.Subjects/methods: A 12-year-old patient (O blood group) with severe hemorrhagictendency was phenotypically and genotypically analyzed; his parents were alsostudied.Results: The proband showed decrease FVIII:C, VWF:RCo/VWF:Ag, and VWF:CB6/VWF:Ag ratios, but normal platelet count, VWF:CB1/VWF:Ag ratio, VWFpp and multimeric pattern, suggesting a VWD2M phenotype. The DDAVP challenge test, compared to controls (VWD2M patients with mutations in VWF-A1 domain), showed lower increase of FVIII:C and VWF:Ag than in heterozygous, but very similar to homozygous control. Two mutations were found in heterozygous and trans presentation: p.Pro1648fs*45 and a novel missense mutation, p.Arg1426Cys. The mother was p.Arg1426Cys heterozygous carrier, with few clinical symptoms. The father was asymptomatic, with no mutations. The p.Pro1648fs*45 was considered an apparent de novo mutation; proband?s AS-PCR revealed mosaicism in the paternal allele. According to the predicted models, p.Arg1426Cys would not be affecting the binding of GPIbα to A1 domain, whereas p.Pro1648fs*45 seems to modify the folding of A2 domain, and in this way, it would affect the binding to GPIbα and type VI collagen. We believe that the combination of these two heterozygous mutations, in a child with O blood group, could result in a defective phenotype enhancer.eCollection 2018 Jan
Fil: Woods, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Paiva Palomino, Juvenal Hernán. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Kempfer, Ana Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Primrose, Debora Marina. Universidad de Morón. Facultad de Agronomía y Ciencias Agroalimentarias; Argentina
Fil: Blanco, Alicia Noemi. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina
Fil: Sánchez Luceros, Analía Gabriela. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Background: Type 2M von Willebrand disease (VWD2M) is usually characterized byVWF:RCo/VWF:Ag<0.6 and normal multimeric profile; desmopressin (DDAVP) challengetest commonly shows poor response of VWF:RCo.Objective: We describe the bleeding tendency and the laboratory phenotype in a patient carrying two heterozygous mutations affecting VWF-A1 domain and VWF-A2domain.Subjects/methods: A 12-year-old patient (O blood group) with severe hemorrhagictendency was phenotypically and genotypically analyzed; his parents were alsostudied.Results: The proband showed decrease FVIII:C, VWF:RCo/VWF:Ag, and VWF:CB6/VWF:Ag ratios, but normal platelet count, VWF:CB1/VWF:Ag ratio, VWFpp and multimeric pattern, suggesting a VWD2M phenotype. The DDAVP challenge test, compared to controls (VWD2M patients with mutations in VWF-A1 domain), showed lower increase of FVIII:C and VWF:Ag than in heterozygous, but very similar to homozygous control. Two mutations were found in heterozygous and trans presentation: p.Pro1648fs*45 and a novel missense mutation, p.Arg1426Cys. The mother was p.Arg1426Cys heterozygous carrier, with few clinical symptoms. The father was asymptomatic, with no mutations. The p.Pro1648fs*45 was considered an apparent de novo mutation; proband?s AS-PCR revealed mosaicism in the paternal allele. According to the predicted models, p.Arg1426Cys would not be affecting the binding of GPIbα to A1 domain, whereas p.Pro1648fs*45 seems to modify the folding of A2 domain, and in this way, it would affect the binding to GPIbα and type VI collagen. We believe that the combination of these two heterozygous mutations, in a child with O blood group, could result in a defective phenotype enhancer.eCollection 2018 Jan
publishDate 2018
dc.date.none.fl_str_mv 2018-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/95515
Woods, Adriana Inés; Paiva Palomino, Juvenal Hernán; Kempfer, Ana Catalina; Primrose, Debora Marina; Blanco, Alicia Noemi; et al.; Combined effects of two mutations in von Willebrand disease 2M phenotype; Wiley; Research and Practice in Thrombosis and Haemostasis; 2; 1; 1-2018; 162-167
2475-0379
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95515
identifier_str_mv Woods, Adriana Inés; Paiva Palomino, Juvenal Hernán; Kempfer, Ana Catalina; Primrose, Debora Marina; Blanco, Alicia Noemi; et al.; Combined effects of two mutations in von Willebrand disease 2M phenotype; Wiley; Research and Practice in Thrombosis and Haemostasis; 2; 1; 1-2018; 162-167
2475-0379
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/rth2.12067
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/rth2.12067
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.001348

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