A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome

The persistent Müllerian duct syndrome (PMDS) is a 46,XY disorder of sexual development characterized by the persistence of Müllerian duct derivatives, uterus and tubes, in otherwise normally masculinized males. The condition, transmitted as a recessive autosomal trait, is usually due to mutations i...

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Detalhes bibliográficos
Autores: Schteingart, Helena Fedora, Picard, Jean Yves, Valeri, Clara, Marshall, Ian, Treton, Dominique, di Clemente, Nathalie, Rey, Rodolfo Alberto, Josso, Nathalie
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/159180
Acesso em linha:http://hdl.handle.net/11336/159180
Access Level:acceso abierto
Palavra-chave:AMH
DSD
UTERUS
TESTIS
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
id AR_5e7265ca8df67b268a2c05aeb4668d63
oai_identifier_str oai:ri.conicet.gov.ar:11336/159180
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
title A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
spellingShingle A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
Schteingart, Helena Fedora
AMH
DSD
UTERUS
TESTIS
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
title_short A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
title_full A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
title_fullStr A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
title_full_unstemmed A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
title_sort A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
dc.creator.none.fl_str_mv Schteingart, Helena Fedora
Picard, Jean Yves
Valeri, Clara
Marshall, Ian
Treton, Dominique
di Clemente, Nathalie
Rey, Rodolfo Alberto
Josso, Nathalie
author Schteingart, Helena Fedora
author_facet Schteingart, Helena Fedora
Picard, Jean Yves
Valeri, Clara
Marshall, Ian
Treton, Dominique
di Clemente, Nathalie
Rey, Rodolfo Alberto
Josso, Nathalie
author_role author
author2 Picard, Jean Yves
Valeri, Clara
Marshall, Ian
Treton, Dominique
di Clemente, Nathalie
Rey, Rodolfo Alberto
Josso, Nathalie
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AMH
DSD
UTERUS
TESTIS
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
topic AMH
DSD
UTERUS
TESTIS
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
description The persistent Müllerian duct syndrome (PMDS) is a 46,XY disorder of sexual development characterized by the persistence of Müllerian duct derivatives, uterus and tubes, in otherwise normally masculinized males. The condition, transmitted as a recessive autosomal trait, is usually due to mutations in either the anti-Müllerian hormone (AMH) gene or its main receptor. Many variants of these genes have been described, all targeting the coding sequences. We report the first case of PMDS due to a regulatory mutation. The AMH promoter contains two binding sites for steroidogenic factor 1 (SF1), one at -102 and the other at -228. Our patient carries a single base deletion at -225, significantly decreasing its capacity for binding SF1, as measured by electrophoresis mobility shift assay. Furthermore, by linking the AMH promoter to the luciferase gene, we show that the transactivation capacity of the promoter is significantly decreased by the mutation, in contrast to disruption of the -102 binding site. To explain the difference in impact we hypothesize that SF1 could partially overcome the lack of binding to the -102 binding site by interacting with a GATA4 molecule linked to a nearby response element. We show that disruption of both the -102 SF1 and the -84 GATA response elements significantly decreases the transactivation capacity of the promoter. In conclusion, we suggest that the distance between mutated SF1 sites and potentially rescuing GATA-binding motifs might play a role in the development of PMDS.
publishDate 2019
dc.date.none.fl_str_mv 2019-06
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/11336/159180
Schteingart, Helena Fedora; Picard, Jean Yves; Valeri, Clara; Marshall, Ian; Treton, Dominique; et al.; A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome; Oxford University Press; Human Molecular Genetics; 28; 19; 6-2019; 3211-3218
0964-6906
1460-2083
CONICET Digital
CONICET
url http://hdl.handle.net/11336/159180
identifier_str_mv Schteingart, Helena Fedora; Picard, Jean Yves; Valeri, Clara; Marshall, Ian; Treton, Dominique; et al.; A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome; Oxford University Press; Human Molecular Genetics; 28; 19; 6-2019; 3211-3218
0964-6906
1460-2083
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddz147/5522632
info:eu-repo/semantics/altIdentifier/doi/10.1093/hmg/ddz147
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
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
_version_ 1799196454529531904
spelling A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndromeSchteingart, Helena FedoraPicard, Jean YvesValeri, ClaraMarshall, IanTreton, Dominiquedi Clemente, NathalieRey, Rodolfo AlbertoJosso, NathalieAMHDSDUTERUSTESTIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The persistent Müllerian duct syndrome (PMDS) is a 46,XY disorder of sexual development characterized by the persistence of Müllerian duct derivatives, uterus and tubes, in otherwise normally masculinized males. The condition, transmitted as a recessive autosomal trait, is usually due to mutations in either the anti-Müllerian hormone (AMH) gene or its main receptor. Many variants of these genes have been described, all targeting the coding sequences. We report the first case of PMDS due to a regulatory mutation. The AMH promoter contains two binding sites for steroidogenic factor 1 (SF1), one at -102 and the other at -228. Our patient carries a single base deletion at -225, significantly decreasing its capacity for binding SF1, as measured by electrophoresis mobility shift assay. Furthermore, by linking the AMH promoter to the luciferase gene, we show that the transactivation capacity of the promoter is significantly decreased by the mutation, in contrast to disruption of the -102 binding site. To explain the difference in impact we hypothesize that SF1 could partially overcome the lack of binding to the -102 binding site by interacting with a GATA4 molecule linked to a nearby response element. We show that disruption of both the -102 SF1 and the -84 GATA response elements significantly decreases the transactivation capacity of the promoter. In conclusion, we suggest that the distance between mutated SF1 sites and potentially rescuing GATA-binding motifs might play a role in the development of PMDS.Fil: Schteingart, Helena Fedora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Picard, Jean Yves. Inserm; Francia. Sorbonne University; FranciaFil: Valeri, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Marshall, Ian. Child Health Institute of New Jersey; Estados UnidosFil: Treton, Dominique. Sorbonne University; Francia. Inserm; FranciaFil: di Clemente, Nathalie. Sorbonne University; Francia. Inserm; FranciaFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Josso, Nathalie. Inserm; Francia. Sorbonne University; FranciaOxford University Press2019-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/159180Schteingart, Helena Fedora; Picard, Jean Yves; Valeri, Clara; Marshall, Ian; Treton, Dominique; et al.; A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome; Oxford University Press; Human Molecular Genetics; 28; 19; 6-2019; 3211-32180964-69061460-2083CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddz147/5522632info:eu-repo/semantics/altIdentifier/doi/10.1093/hmg/ddz147info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:28:28Zoai:ri.conicet.gov.ar:11336/159180instacron: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:34982024-05-08 14:28:28.845CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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