Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort

Autores
Touzon, María Sol; Perez Garrido, Natalia Isabel; Marino, Roxana Marcela; Ramirez, Pablo; Costanzo, Mariana; Guercio, Gabriela Viviana; Berensztein, Esperanza Beatriz; Rivarola, Marco Aurelio; Belgorosky, Alicia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: The aim of this study was the molecular characterization of the AR gene as the cause of 46,XY disorder in our population. Methods: We studied 41, non related, 46,XY disorder of sexual differentiation index cases, having characteristics consistent with androgen insensivity syndrome (AIS). Genomic DNA was isolated from peripheral blood leukocytes of all patients and 25 family members from 17 non-related families. Results: The AR gene analysis revealed an abnormal sequence in 58.5% of the index patients. All of the complete AIS (CAIS) cases were genetically confirmed, while in the partial form (PAIS) a mutation in AR was detected in only 13 (43.3%). Molecular studies revealed other affected or carrier relatives in 87% of the index cases. The AR mutations were found spread along the whole coding sequence, with a higher prevalence in the ligand binding domain. Nine out of 23 (39%) AR mutations were novel. In 17% of patients with detected AR mutations, somatic mosaicism was detected in leucocyte DNA. In our cohort, long-term follow up gender dysphoria, raised as male or female, was not found. Finally, in suspected PAIS, the identification of AR mutation occurred significantly less than in CAIS patients. Conclusion: Improved knowledge of the components of the AR complex and signaling network might contribute to long term outcome and genetic counseling in AIS patients.
Fil: Touzon, María Sol. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Perez Garrido, Natalia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Marino, Roxana Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Ramirez, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Costanzo, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Guercio, Gabriela Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Berensztein, Esperanza Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Rivarola, Marco Aurelio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
XY DISORDERS OF SEX DEVELOPMENT
ANDROGEN INSENSITIVITY SÍNDROME
ANDROGEN RECEPTOR GENE MUTATIONS
MOSAICISM
CLINICAL PHENOTYPE
46
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:11336/121604
Acceder
id CONICETDig_08ae8a52bbc5db279ce73acd38be106c
oai_identifier_str oai:ri.conicet.gov.ar:11336/121604
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohortTouzon, María SolPerez Garrido, Natalia IsabelMarino, Roxana MarcelaRamirez, PabloCostanzo, MarianaGuercio, Gabriela VivianaBerensztein, Esperanza BeatrizRivarola, Marco AurelioBelgorosky, AliciaXY DISORDERS OF SEX DEVELOPMENTANDROGEN INSENSITIVITY SÍNDROMEANDROGEN RECEPTOR GENE MUTATIONSMOSAICISMCLINICAL PHENOTYPE46https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Objective: The aim of this study was the molecular characterization of the AR gene as the cause of 46,XY disorder in our population. Methods: We studied 41, non related, 46,XY disorder of sexual differentiation index cases, having characteristics consistent with androgen insensivity syndrome (AIS). Genomic DNA was isolated from peripheral blood leukocytes of all patients and 25 family members from 17 non-related families. Results: The AR gene analysis revealed an abnormal sequence in 58.5% of the index patients. All of the complete AIS (CAIS) cases were genetically confirmed, while in the partial form (PAIS) a mutation in AR was detected in only 13 (43.3%). Molecular studies revealed other affected or carrier relatives in 87% of the index cases. The AR mutations were found spread along the whole coding sequence, with a higher prevalence in the ligand binding domain. Nine out of 23 (39%) AR mutations were novel. In 17% of patients with detected AR mutations, somatic mosaicism was detected in leucocyte DNA. In our cohort, long-term follow up gender dysphoria, raised as male or female, was not found. Finally, in suspected PAIS, the identification of AR mutation occurred significantly less than in CAIS patients. Conclusion: Improved knowledge of the components of the AR complex and signaling network might contribute to long term outcome and genetic counseling in AIS patients.Fil: Touzon, María Sol. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perez Garrido, Natalia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Marino, Roxana Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ramirez, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Costanzo, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Guercio, Gabriela Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Berensztein, Esperanza Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Rivarola, Marco Aurelio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaGalenos Yayincilik2019-03info: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/11336/121604Touzon, María Sol; Perez Garrido, Natalia Isabel; Marino, Roxana Marcela; Ramirez, Pablo; Costanzo, Mariana; et al.; Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort; Galenos Yayincilik; Journal of Clinical Research in Pediatric Endocrinology; 11; 1; 3-2019; 24-331308-57271308-5735CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://cms.galenos.com.tr/Uploads/Article_19687/JCRPE-0-0-En.pdfinfo:eu-repo/semantics/altIdentifier/doi/10.4274/jcrpe.galenos.2018.2018.0185info:eu-repo/semantics/altIdentifier/url/http://www.jcrpe.org/archives/archive-detail/article-preview/androgen-nsensitivity-syndrome-clinical-phenotype-/19687info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:17:50Zoai:ri.conicet.gov.ar:11336/121604instacron: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 10:17:51.176CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort
title Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort
spellingShingle Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort
Touzon, María Sol
XY DISORDERS OF SEX DEVELOPMENT
ANDROGEN INSENSITIVITY SÍNDROME
ANDROGEN RECEPTOR GENE MUTATIONS
MOSAICISM
CLINICAL PHENOTYPE
46
title_short Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort
title_full Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort
title_fullStr Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort
title_full_unstemmed Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort
title_sort Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort
dc.creator.none.fl_str_mv Touzon, María Sol
Perez Garrido, Natalia Isabel
Marino, Roxana Marcela
Ramirez, Pablo
Costanzo, Mariana
Guercio, Gabriela Viviana
Berensztein, Esperanza Beatriz
Rivarola, Marco Aurelio
Belgorosky, Alicia
author Touzon, María Sol
author_facet Touzon, María Sol
Perez Garrido, Natalia Isabel
Marino, Roxana Marcela
Ramirez, Pablo
Costanzo, Mariana
Guercio, Gabriela Viviana
Berensztein, Esperanza Beatriz
Rivarola, Marco Aurelio
Belgorosky, Alicia
author_role author
author2 Perez Garrido, Natalia Isabel
Marino, Roxana Marcela
Ramirez, Pablo
Costanzo, Mariana
Guercio, Gabriela Viviana
Berensztein, Esperanza Beatriz
Rivarola, Marco Aurelio
Belgorosky, Alicia
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv XY DISORDERS OF SEX DEVELOPMENT
ANDROGEN INSENSITIVITY SÍNDROME
ANDROGEN RECEPTOR GENE MUTATIONS
MOSAICISM
CLINICAL PHENOTYPE
46
topic XY DISORDERS OF SEX DEVELOPMENT
ANDROGEN INSENSITIVITY SÍNDROME
ANDROGEN RECEPTOR GENE MUTATIONS
MOSAICISM
CLINICAL PHENOTYPE
46
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: The aim of this study was the molecular characterization of the AR gene as the cause of 46,XY disorder in our population. Methods: We studied 41, non related, 46,XY disorder of sexual differentiation index cases, having characteristics consistent with androgen insensivity syndrome (AIS). Genomic DNA was isolated from peripheral blood leukocytes of all patients and 25 family members from 17 non-related families. Results: The AR gene analysis revealed an abnormal sequence in 58.5% of the index patients. All of the complete AIS (CAIS) cases were genetically confirmed, while in the partial form (PAIS) a mutation in AR was detected in only 13 (43.3%). Molecular studies revealed other affected or carrier relatives in 87% of the index cases. The AR mutations were found spread along the whole coding sequence, with a higher prevalence in the ligand binding domain. Nine out of 23 (39%) AR mutations were novel. In 17% of patients with detected AR mutations, somatic mosaicism was detected in leucocyte DNA. In our cohort, long-term follow up gender dysphoria, raised as male or female, was not found. Finally, in suspected PAIS, the identification of AR mutation occurred significantly less than in CAIS patients. Conclusion: Improved knowledge of the components of the AR complex and signaling network might contribute to long term outcome and genetic counseling in AIS patients.
Fil: Touzon, María Sol. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Perez Garrido, Natalia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Marino, Roxana Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Ramirez, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Costanzo, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Guercio, Gabriela Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Berensztein, Esperanza Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Rivarola, Marco Aurelio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Objective: The aim of this study was the molecular characterization of the AR gene as the cause of 46,XY disorder in our population. Methods: We studied 41, non related, 46,XY disorder of sexual differentiation index cases, having characteristics consistent with androgen insensivity syndrome (AIS). Genomic DNA was isolated from peripheral blood leukocytes of all patients and 25 family members from 17 non-related families. Results: The AR gene analysis revealed an abnormal sequence in 58.5% of the index patients. All of the complete AIS (CAIS) cases were genetically confirmed, while in the partial form (PAIS) a mutation in AR was detected in only 13 (43.3%). Molecular studies revealed other affected or carrier relatives in 87% of the index cases. The AR mutations were found spread along the whole coding sequence, with a higher prevalence in the ligand binding domain. Nine out of 23 (39%) AR mutations were novel. In 17% of patients with detected AR mutations, somatic mosaicism was detected in leucocyte DNA. In our cohort, long-term follow up gender dysphoria, raised as male or female, was not found. Finally, in suspected PAIS, the identification of AR mutation occurred significantly less than in CAIS patients. Conclusion: Improved knowledge of the components of the AR complex and signaling network might contribute to long term outcome and genetic counseling in AIS patients.
publishDate 2019
dc.date.none.fl_str_mv 2019-03
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/11336/121604
Touzon, María Sol; Perez Garrido, Natalia Isabel; Marino, Roxana Marcela; Ramirez, Pablo; Costanzo, Mariana; et al.; Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort; Galenos Yayincilik; Journal of Clinical Research in Pediatric Endocrinology; 11; 1; 3-2019; 24-33
1308-5727
1308-5735
CONICET Digital
CONICET
url http://hdl.handle.net/11336/121604
identifier_str_mv Touzon, María Sol; Perez Garrido, Natalia Isabel; Marino, Roxana Marcela; Ramirez, Pablo; Costanzo, Mariana; et al.; Androgen insensitivity syndrome: Clinical phenotype and molecular analysis in a single tertiary center cohort; Galenos Yayincilik; Journal of Clinical Research in Pediatric Endocrinology; 11; 1; 3-2019; 24-33
1308-5727
1308-5735
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://cms.galenos.com.tr/Uploads/Article_19687/JCRPE-0-0-En.pdf
info:eu-repo/semantics/altIdentifier/doi/10.4274/jcrpe.galenos.2018.2018.0185
info:eu-repo/semantics/altIdentifier/url/http://www.jcrpe.org/archives/archive-detail/article-preview/androgen-nsensitivity-syndrome-clinical-phenotype-/19687
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
dc.publisher.none.fl_str_mv Galenos Yayincilik
publisher.none.fl_str_mv Galenos Yayincilik
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 13.070432

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