A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy
- Autores
- Calderazzo, Julio César; Kempfer, Ana Catalina; Powazniak, Yanina Paola; Lopez, Lleana R.; Sánchez Luceros, Analía Gabriela; Woods, Adriana Inés; Lazzari, María Ángela
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microvascular thrombosis, often associated with deficiency of ADAMTS13 activity. Hereditary TTP has been linked to mutations in the ADAMTS13 gene whereas the inhibition of ADAMTS13 activity by autoimmune antibodies has been associated with acquired TTP. We report the case of a woman with deficiency of ADAMTS13 activity that had been asymptomatic until her first severe TTP episode during her first pregnancy. Genetic analysis revealed a non described missense mutation of ADAMTS13. This mutation resulted in an aspartic acid to valine substitution (D1362V). To verify the mechanism of ADAMTS13 deficiency in this patient, the wild type and the D1362V ADAMTS13 mutant construct was expressed in HEK 293 cells. The D1362V substitution led to a defect of secretion (ADAMTS13 antigen level=8±3%, ADAMTS13 activity=0% in culture media), causing intracellular accumulation of the protease (ADAMTS13 antigen level=133±5%, ADAMTS13 activity=129±13%) compared to wild-type (WT) ADAMTS13 (ADAMTS13 antigen and activity=100%). The results showed that D1362V mutation in the second CUB (CUB-2) domain, encoded by exon 29, induces an ADAMTS13 plasmatic deficiency due to reduced secretion of the protease into the circulation. Our data suggested that the CUB-2 domain encoded by exon 29 is particularly important for ADAMTS13 secretion. Apparently, this severe ADAMTS13 plasmatic deficiency did not manage to lead to clinical manifestations given that the TTP triggering event was related to her first pregnancy.
Fil: Calderazzo, Julio César. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kempfer, Ana Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Powazniak, Yanina Paola. Ministerio de Ciencia, Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica. Fondo para la Investigación Científica y Tecnológica; Argentina
Fil: Lopez, Lleana R.. Hemobanco San Miguel de Tucuman; Argentina
Fil: Sánchez Luceros, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Woods, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina - Materia
-
Thrombotic Thrombocytopenic Purpura
Adamts13
Pregnancy
Cub-2 Domain
Site-Directed Mutagenesis - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/53312
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/53312 |
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network_name_str |
CONICET Digital (CONICET) |
spelling |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancyCalderazzo, Julio CésarKempfer, Ana CatalinaPowazniak, Yanina PaolaLopez, Lleana R.Sánchez Luceros, Analía GabrielaWoods, Adriana InésLazzari, María ÁngelaThrombotic Thrombocytopenic PurpuraAdamts13PregnancyCub-2 DomainSite-Directed Mutagenesishttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microvascular thrombosis, often associated with deficiency of ADAMTS13 activity. Hereditary TTP has been linked to mutations in the ADAMTS13 gene whereas the inhibition of ADAMTS13 activity by autoimmune antibodies has been associated with acquired TTP. We report the case of a woman with deficiency of ADAMTS13 activity that had been asymptomatic until her first severe TTP episode during her first pregnancy. Genetic analysis revealed a non described missense mutation of ADAMTS13. This mutation resulted in an aspartic acid to valine substitution (D1362V). To verify the mechanism of ADAMTS13 deficiency in this patient, the wild type and the D1362V ADAMTS13 mutant construct was expressed in HEK 293 cells. The D1362V substitution led to a defect of secretion (ADAMTS13 antigen level=8±3%, ADAMTS13 activity=0% in culture media), causing intracellular accumulation of the protease (ADAMTS13 antigen level=133±5%, ADAMTS13 activity=129±13%) compared to wild-type (WT) ADAMTS13 (ADAMTS13 antigen and activity=100%). The results showed that D1362V mutation in the second CUB (CUB-2) domain, encoded by exon 29, induces an ADAMTS13 plasmatic deficiency due to reduced secretion of the protease into the circulation. Our data suggested that the CUB-2 domain encoded by exon 29 is particularly important for ADAMTS13 secretion. Apparently, this severe ADAMTS13 plasmatic deficiency did not manage to lead to clinical manifestations given that the TTP triggering event was related to her first pregnancy.Fil: Calderazzo, Julio César. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kempfer, Ana Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Powazniak, Yanina Paola. Ministerio de Ciencia, Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica. Fondo para la Investigación Científica y Tecnológica; ArgentinaFil: Lopez, Lleana R.. Hemobanco San Miguel de Tucuman; ArgentinaFil: Sánchez Luceros, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Woods, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaSchattauer Gmbh-Verlag Medizin Naturwissenschaften2012-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53312Calderazzo, Julio César; Kempfer, Ana Catalina; Powazniak, Yanina Paola; Lopez, Lleana R.; Sánchez Luceros, Analía Gabriela; et al.; A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy; Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 108; 2; 8-2012; 401-4030340-6245CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1160/TH11-11-0783info:eu-repo/semantics/altIdentifier/url/https://www.thieme-connect.de/DOI/DOI?10.1160/TH11-11-0783info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:34:56Zoai:ri.conicet.gov.ar:11336/53312instacron: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:34982025-09-29 10:34:57.183CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy |
title |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy |
spellingShingle |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy Calderazzo, Julio César Thrombotic Thrombocytopenic Purpura Adamts13 Pregnancy Cub-2 Domain Site-Directed Mutagenesis |
title_short |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy |
title_full |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy |
title_fullStr |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy |
title_full_unstemmed |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy |
title_sort |
A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy |
dc.creator.none.fl_str_mv |
Calderazzo, Julio César Kempfer, Ana Catalina Powazniak, Yanina Paola Lopez, Lleana R. Sánchez Luceros, Analía Gabriela Woods, Adriana Inés Lazzari, María Ángela |
author |
Calderazzo, Julio César |
author_facet |
Calderazzo, Julio César Kempfer, Ana Catalina Powazniak, Yanina Paola Lopez, Lleana R. Sánchez Luceros, Analía Gabriela Woods, Adriana Inés Lazzari, María Ángela |
author_role |
author |
author2 |
Kempfer, Ana Catalina Powazniak, Yanina Paola Lopez, Lleana R. Sánchez Luceros, Analía Gabriela Woods, Adriana Inés Lazzari, María Ángela |
author2_role |
author author author author author author |
dc.subject.none.fl_str_mv |
Thrombotic Thrombocytopenic Purpura Adamts13 Pregnancy Cub-2 Domain Site-Directed Mutagenesis |
topic |
Thrombotic Thrombocytopenic Purpura Adamts13 Pregnancy Cub-2 Domain Site-Directed Mutagenesis |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microvascular thrombosis, often associated with deficiency of ADAMTS13 activity. Hereditary TTP has been linked to mutations in the ADAMTS13 gene whereas the inhibition of ADAMTS13 activity by autoimmune antibodies has been associated with acquired TTP. We report the case of a woman with deficiency of ADAMTS13 activity that had been asymptomatic until her first severe TTP episode during her first pregnancy. Genetic analysis revealed a non described missense mutation of ADAMTS13. This mutation resulted in an aspartic acid to valine substitution (D1362V). To verify the mechanism of ADAMTS13 deficiency in this patient, the wild type and the D1362V ADAMTS13 mutant construct was expressed in HEK 293 cells. The D1362V substitution led to a defect of secretion (ADAMTS13 antigen level=8±3%, ADAMTS13 activity=0% in culture media), causing intracellular accumulation of the protease (ADAMTS13 antigen level=133±5%, ADAMTS13 activity=129±13%) compared to wild-type (WT) ADAMTS13 (ADAMTS13 antigen and activity=100%). The results showed that D1362V mutation in the second CUB (CUB-2) domain, encoded by exon 29, induces an ADAMTS13 plasmatic deficiency due to reduced secretion of the protease into the circulation. Our data suggested that the CUB-2 domain encoded by exon 29 is particularly important for ADAMTS13 secretion. Apparently, this severe ADAMTS13 plasmatic deficiency did not manage to lead to clinical manifestations given that the TTP triggering event was related to her first pregnancy. Fil: Calderazzo, Julio César. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Kempfer, Ana Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Powazniak, Yanina Paola. Ministerio de Ciencia, Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica. Fondo para la Investigación Científica y Tecnológica; Argentina Fil: Lopez, Lleana R.. Hemobanco San Miguel de Tucuman; Argentina Fil: Sánchez Luceros, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Woods, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina |
description |
Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microvascular thrombosis, often associated with deficiency of ADAMTS13 activity. Hereditary TTP has been linked to mutations in the ADAMTS13 gene whereas the inhibition of ADAMTS13 activity by autoimmune antibodies has been associated with acquired TTP. We report the case of a woman with deficiency of ADAMTS13 activity that had been asymptomatic until her first severe TTP episode during her first pregnancy. Genetic analysis revealed a non described missense mutation of ADAMTS13. This mutation resulted in an aspartic acid to valine substitution (D1362V). To verify the mechanism of ADAMTS13 deficiency in this patient, the wild type and the D1362V ADAMTS13 mutant construct was expressed in HEK 293 cells. The D1362V substitution led to a defect of secretion (ADAMTS13 antigen level=8±3%, ADAMTS13 activity=0% in culture media), causing intracellular accumulation of the protease (ADAMTS13 antigen level=133±5%, ADAMTS13 activity=129±13%) compared to wild-type (WT) ADAMTS13 (ADAMTS13 antigen and activity=100%). The results showed that D1362V mutation in the second CUB (CUB-2) domain, encoded by exon 29, induces an ADAMTS13 plasmatic deficiency due to reduced secretion of the protease into the circulation. Our data suggested that the CUB-2 domain encoded by exon 29 is particularly important for ADAMTS13 secretion. Apparently, this severe ADAMTS13 plasmatic deficiency did not manage to lead to clinical manifestations given that the TTP triggering event was related to her first pregnancy. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-08 |
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/11336/53312 Calderazzo, Julio César; Kempfer, Ana Catalina; Powazniak, Yanina Paola; Lopez, Lleana R.; Sánchez Luceros, Analía Gabriela; et al.; A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy; Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 108; 2; 8-2012; 401-403 0340-6245 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/53312 |
identifier_str_mv |
Calderazzo, Julio César; Kempfer, Ana Catalina; Powazniak, Yanina Paola; Lopez, Lleana R.; Sánchez Luceros, Analía Gabriela; et al.; A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy; Schattauer Gmbh-Verlag Medizin Naturwissenschaften; Thrombosis and Haemostasis; 108; 2; 8-2012; 401-403 0340-6245 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1160/TH11-11-0783 info:eu-repo/semantics/altIdentifier/url/https://www.thieme-connect.de/DOI/DOI?10.1160/TH11-11-0783 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Schattauer Gmbh-Verlag Medizin Naturwissenschaften |
publisher.none.fl_str_mv |
Schattauer Gmbh-Verlag Medizin Naturwissenschaften |
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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1844614366861721600 |
score |
13.070432 |