Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability

Autores
Dauber, Andrew; Muñoz Calvo, María T.; Barrios, Vicente; Domene, Horacio Mario; Kloverpris, Soren; Serra Juhé, Clara; Desikan, Vardhini; Pozo, Jesús; Muzumdar, Radhika; Martos Moreno, Gabriel Á; Hawkins, Federico; Jasper, Hector Guillermo; Conover, Cheryl A.; Frystyk, Jan; Yakar, Shoshana; Hwa, Vivian; Chowen, Julie A.; Oxvig, Claus; Rosenfeld, Ron G.; Pérez-Jurado, Luis A.; Argente, Jesús
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the met alloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs.
Fil: Dauber, Andrew. Cincinnati Children's Hospital Medical Center; Estados Unidos
Fil: Muñoz Calvo, María T.. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Barrios, Vicente. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Kloverpris, Soren. University Aarhus; Dinamarca
Fil: Serra Juhé, Clara. Universitat Pompeu Fabra; España
Fil: Desikan, Vardhini. New York Medical College; Estados Unidos
Fil: Pozo, Jesús. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Muzumdar, Radhika. University Of Pittsburgh Medical Center, Children's Hospital Of Pittsburgh; Estados Unidos
Fil: Martos Moreno, Gabriel Á. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Hawkins, Federico. Universidad Complutense de Madrid; España
Fil: Jasper, Hector Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Conover, Cheryl A.. Mayo Clinic; Estados Unidos
Fil: Frystyk, Jan. University Aarhus; Dinamarca. Arhus Universitets Hospital; Dinamarca
Fil: Yakar, Shoshana. Nyu College Of Dentistry; Estados Unidos
Fil: Hwa, Vivian. Cincinnati Children's Hospital Medical Center; Estados Unidos
Fil: Chowen, Julie A.. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Oxvig, Claus. University Aarhus; Dinamarca
Fil: Rosenfeld, Ron G.. Oregon Health And Science University; Estados Unidos
Fil: Pérez-Jurado, Luis A.. Universitat Pompeu Fabra; España
Fil: Argente, Jesús. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Materia
BONE
DELAYED GROWTH
GROWTH HORMONE
IGF BIOAVAILABILITY
IGF-BINDING PROTEINS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/54510
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/54510
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availabilityDauber, AndrewMuñoz Calvo, María T.Barrios, VicenteDomene, Horacio MarioKloverpris, SorenSerra Juhé, ClaraDesikan, VardhiniPozo, JesúsMuzumdar, RadhikaMartos Moreno, Gabriel ÁHawkins, FedericoJasper, Hector GuillermoConover, Cheryl A.Frystyk, JanYakar, ShoshanaHwa, VivianChowen, Julie A.Oxvig, ClausRosenfeld, Ron G.Pérez-Jurado, Luis A.Argente, JesúsBONEDELAYED GROWTHGROWTH HORMONEIGF BIOAVAILABILITYIGF-BINDING PROTEINShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the met alloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs.Fil: Dauber, Andrew. Cincinnati Children's Hospital Medical Center; Estados UnidosFil: Muñoz Calvo, María T.. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; EspañaFil: Barrios, Vicente. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; EspañaFil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Kloverpris, Soren. University Aarhus; DinamarcaFil: Serra Juhé, Clara. Universitat Pompeu Fabra; EspañaFil: Desikan, Vardhini. New York Medical College; Estados UnidosFil: Pozo, Jesús. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; EspañaFil: Muzumdar, Radhika. University Of Pittsburgh Medical Center, Children's Hospital Of Pittsburgh; Estados UnidosFil: Martos Moreno, Gabriel Á. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; EspañaFil: Hawkins, Federico. Universidad Complutense de Madrid; EspañaFil: Jasper, Hector Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Conover, Cheryl A.. Mayo Clinic; Estados UnidosFil: Frystyk, Jan. University Aarhus; Dinamarca. Arhus Universitets Hospital; DinamarcaFil: Yakar, Shoshana. Nyu College Of Dentistry; Estados UnidosFil: Hwa, Vivian. Cincinnati Children's Hospital Medical Center; Estados UnidosFil: Chowen, Julie A.. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; EspañaFil: Oxvig, Claus. University Aarhus; DinamarcaFil: Rosenfeld, Ron G.. Oregon Health And Science University; Estados UnidosFil: Pérez-Jurado, Luis A.. Universitat Pompeu Fabra; EspañaFil: Argente, Jesús. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; EspañaWiley Blackwell Publishing, Inc2016-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/54510Dauber, Andrew; Muñoz Calvo, María T.; Barrios, Vicente; Domene, Horacio Mario; Kloverpris, Soren; et al.; Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability; Wiley Blackwell Publishing, Inc; Embo Molecular Medicine; 8; 4; 4-2016; 363-3741757-46841757-4676CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.15252/emmm.201506106info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:36Zoai:ri.conicet.gov.ar:11336/54510instacron: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:34982025-09-03 10:01:36.545CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability
title Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability
spellingShingle Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability
Dauber, Andrew
BONE
DELAYED GROWTH
GROWTH HORMONE
IGF BIOAVAILABILITY
IGF-BINDING PROTEINS
title_short Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability
title_full Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability
title_fullStr Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability
title_full_unstemmed Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability
title_sort Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability
dc.creator.none.fl_str_mv Dauber, Andrew
Muñoz Calvo, María T.
Barrios, Vicente
Domene, Horacio Mario
Kloverpris, Soren
Serra Juhé, Clara
Desikan, Vardhini
Pozo, Jesús
Muzumdar, Radhika
Martos Moreno, Gabriel Á
Hawkins, Federico
Jasper, Hector Guillermo
Conover, Cheryl A.
Frystyk, Jan
Yakar, Shoshana
Hwa, Vivian
Chowen, Julie A.
Oxvig, Claus
Rosenfeld, Ron G.
Pérez-Jurado, Luis A.
Argente, Jesús
author Dauber, Andrew
author_facet Dauber, Andrew
Muñoz Calvo, María T.
Barrios, Vicente
Domene, Horacio Mario
Kloverpris, Soren
Serra Juhé, Clara
Desikan, Vardhini
Pozo, Jesús
Muzumdar, Radhika
Martos Moreno, Gabriel Á
Hawkins, Federico
Jasper, Hector Guillermo
Conover, Cheryl A.
Frystyk, Jan
Yakar, Shoshana
Hwa, Vivian
Chowen, Julie A.
Oxvig, Claus
Rosenfeld, Ron G.
Pérez-Jurado, Luis A.
Argente, Jesús
author_role author
author2 Muñoz Calvo, María T.
Barrios, Vicente
Domene, Horacio Mario
Kloverpris, Soren
Serra Juhé, Clara
Desikan, Vardhini
Pozo, Jesús
Muzumdar, Radhika
Martos Moreno, Gabriel Á
Hawkins, Federico
Jasper, Hector Guillermo
Conover, Cheryl A.
Frystyk, Jan
Yakar, Shoshana
Hwa, Vivian
Chowen, Julie A.
Oxvig, Claus
Rosenfeld, Ron G.
Pérez-Jurado, Luis A.
Argente, Jesús
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BONE
DELAYED GROWTH
GROWTH HORMONE
IGF BIOAVAILABILITY
IGF-BINDING PROTEINS
topic BONE
DELAYED GROWTH
GROWTH HORMONE
IGF BIOAVAILABILITY
IGF-BINDING PROTEINS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the met alloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs.
Fil: Dauber, Andrew. Cincinnati Children's Hospital Medical Center; Estados Unidos
Fil: Muñoz Calvo, María T.. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Barrios, Vicente. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Kloverpris, Soren. University Aarhus; Dinamarca
Fil: Serra Juhé, Clara. Universitat Pompeu Fabra; España
Fil: Desikan, Vardhini. New York Medical College; Estados Unidos
Fil: Pozo, Jesús. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Muzumdar, Radhika. University Of Pittsburgh Medical Center, Children's Hospital Of Pittsburgh; Estados Unidos
Fil: Martos Moreno, Gabriel Á. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Hawkins, Federico. Universidad Complutense de Madrid; España
Fil: Jasper, Hector Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Conover, Cheryl A.. Mayo Clinic; Estados Unidos
Fil: Frystyk, Jan. University Aarhus; Dinamarca. Arhus Universitets Hospital; Dinamarca
Fil: Yakar, Shoshana. Nyu College Of Dentistry; Estados Unidos
Fil: Hwa, Vivian. Cincinnati Children's Hospital Medical Center; Estados Unidos
Fil: Chowen, Julie A.. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
Fil: Oxvig, Claus. University Aarhus; Dinamarca
Fil: Rosenfeld, Ron G.. Oregon Health And Science University; Estados Unidos
Fil: Pérez-Jurado, Luis A.. Universitat Pompeu Fabra; España
Fil: Argente, Jesús. Hospital Infantil Universitario Niño Jesus de Madrid; España. Instituto de Salud Carlos III; España
description Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the met alloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs.
publishDate 2016
dc.date.none.fl_str_mv 2016-04
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/11336/54510
Dauber, Andrew; Muñoz Calvo, María T.; Barrios, Vicente; Domene, Horacio Mario; Kloverpris, Soren; et al.; Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability; Wiley Blackwell Publishing, Inc; Embo Molecular Medicine; 8; 4; 4-2016; 363-374
1757-4684
1757-4676
CONICET Digital
CONICET
url http://hdl.handle.net/11336/54510
identifier_str_mv Dauber, Andrew; Muñoz Calvo, María T.; Barrios, Vicente; Domene, Horacio Mario; Kloverpris, Soren; et al.; Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability; Wiley Blackwell Publishing, Inc; Embo Molecular Medicine; 8; 4; 4-2016; 363-374
1757-4684
1757-4676
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.15252/emmm.201506106
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
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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 13.13397

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