Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect
- Autores
- Marino, Roxana Marcela; Garrido, Natalia Perez; Costanzo, Mariana; Guercio, Gabriela Viviana; Juanes, Matías Hernan; Rocco, Carlos Alberto; Ramirez, Pablo; Warman, Diana M.; Ciaccio, Marta; Pena, Gladys; Feyling, José García; Miras, Mirta Beatriz; Rivarola, Marco Aurelio; Belgorosky, Alicia; Saraco, Nora Isabel
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Context: Aromatase is the key enzyme for estrogen biosynthesis and is encoded by the CYP19A1 gene. Since 1991, several molecular CYP19A1 gene alterations associated with aromatase deficiency have been described in both sexes. Objective: The objective of the study was to detect CYP19A1 mutations in five aromatasedeficient 46, XX patients, to describe the clinical follow-up from birth to puberty and to perform haplotype analysis associated with the high-frequency c.628G>A splice mutation in Argentinean patients. Design: The design of the study was the sequencing of the coding and flanking intronic regions of the CYP19A1 gene in all patients and parents. Haplotype analysis of patients carrying the c.628G>A mutation was also performed. Patients: Clinical and biochemical findings in five new cases and one previously reported female aromatase-deficient patient (46, XX) are described. All patients presented with ambiguous genitalia at birth. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency as well as other steroidogenic defects were ruled out. Results: Phenotypic variability among the affected patients was found during follow-up. Direct sequencing of the CYP19A1 gene from genomic DNA revealed one novel mutation (c.574C>T) in two patients. In silico analysis predicted the c.574C>T mutation to be probably damaging. Four of six nonrelated patients presented with the c.628G>A splice mutation. Haplotype analysis showed that the c.628G>A splice mutation is associated with the same haplotype in our population. Conclusions: Increased knowledge on phenotypical variability found in female aromatase-deficient patients is useful to improve the detection rate in this disorder. In our population, a genetic founder defect has probably contributed to an increase in the incidence of the c.628G>A splice mutation.
Fil: Marino, Roxana Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Garrido, Natalia Perez. 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: Juanes, Matías Hernan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rocco, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ramirez, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Warman, Diana M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Ciaccio, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Pena, Gladys. Hospital Infantil Municipal de Cordoba; Argentina
Fil: Feyling, José García. Hospital Regional de Concepcion; Argentina
Fil: Miras, Mirta Beatriz. Hospital de Ninos de la Santisima Trinidad; 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
Fil: Saraco, Nora Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina - Materia
-
Aromatase
Aromatase Deficiency
Founder Effect - 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:11336/37138
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Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effectMarino, Roxana MarcelaGarrido, Natalia PerezCostanzo, MarianaGuercio, Gabriela VivianaJuanes, Matías HernanRocco, Carlos AlbertoRamirez, PabloWarman, Diana M.Ciaccio, MartaPena, GladysFeyling, José GarcíaMiras, Mirta BeatrizRivarola, Marco AurelioBelgorosky, AliciaSaraco, Nora IsabelAromataseAromatase DeficiencyFounder Effecthttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Context: Aromatase is the key enzyme for estrogen biosynthesis and is encoded by the CYP19A1 gene. Since 1991, several molecular CYP19A1 gene alterations associated with aromatase deficiency have been described in both sexes. Objective: The objective of the study was to detect CYP19A1 mutations in five aromatasedeficient 46, XX patients, to describe the clinical follow-up from birth to puberty and to perform haplotype analysis associated with the high-frequency c.628G>A splice mutation in Argentinean patients. Design: The design of the study was the sequencing of the coding and flanking intronic regions of the CYP19A1 gene in all patients and parents. Haplotype analysis of patients carrying the c.628G>A mutation was also performed. Patients: Clinical and biochemical findings in five new cases and one previously reported female aromatase-deficient patient (46, XX) are described. All patients presented with ambiguous genitalia at birth. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency as well as other steroidogenic defects were ruled out. Results: Phenotypic variability among the affected patients was found during follow-up. Direct sequencing of the CYP19A1 gene from genomic DNA revealed one novel mutation (c.574C>T) in two patients. In silico analysis predicted the c.574C>T mutation to be probably damaging. Four of six nonrelated patients presented with the c.628G>A splice mutation. Haplotype analysis showed that the c.628G>A splice mutation is associated with the same haplotype in our population. Conclusions: Increased knowledge on phenotypical variability found in female aromatase-deficient patients is useful to improve the detection rate in this disorder. In our population, a genetic founder defect has probably contributed to an increase in the incidence of the c.628G>A splice mutation.Fil: Marino, Roxana Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Garrido, Natalia Perez. 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: Juanes, Matías Hernan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rocco, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ramirez, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Warman, Diana M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ciaccio, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Pena, Gladys. Hospital Infantil Municipal de Cordoba; ArgentinaFil: Feyling, José García. Hospital Regional de Concepcion; ArgentinaFil: Miras, Mirta Beatriz. Hospital de Ninos de la Santisima Trinidad; 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; ArgentinaFil: Saraco, Nora Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaEndocrine Society2015-02info: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/11336/37138Marino, Roxana Marcela; Garrido, Natalia Perez; Costanzo, Mariana; Guercio, Gabriela Viviana; Juanes, Matías Hernan; et al.; Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 100; 2; 2-2015; E301-E3070021-972XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1210/jc.2014-2967info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jcem/article/100/2/E301/2814966info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:33:45Zoai:ri.conicet.gov.ar:11336/37138instacron: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 10:33:45.508CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect |
title |
Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect |
spellingShingle |
Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect Marino, Roxana Marcela Aromatase Aromatase Deficiency Founder Effect |
title_short |
Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect |
title_full |
Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect |
title_fullStr |
Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect |
title_full_unstemmed |
Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect |
title_sort |
Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect |
dc.creator.none.fl_str_mv |
Marino, Roxana Marcela Garrido, Natalia Perez Costanzo, Mariana Guercio, Gabriela Viviana Juanes, Matías Hernan Rocco, Carlos Alberto Ramirez, Pablo Warman, Diana M. Ciaccio, Marta Pena, Gladys Feyling, José García Miras, Mirta Beatriz Rivarola, Marco Aurelio Belgorosky, Alicia Saraco, Nora Isabel |
author |
Marino, Roxana Marcela |
author_facet |
Marino, Roxana Marcela Garrido, Natalia Perez Costanzo, Mariana Guercio, Gabriela Viviana Juanes, Matías Hernan Rocco, Carlos Alberto Ramirez, Pablo Warman, Diana M. Ciaccio, Marta Pena, Gladys Feyling, José García Miras, Mirta Beatriz Rivarola, Marco Aurelio Belgorosky, Alicia Saraco, Nora Isabel |
author_role |
author |
author2 |
Garrido, Natalia Perez Costanzo, Mariana Guercio, Gabriela Viviana Juanes, Matías Hernan Rocco, Carlos Alberto Ramirez, Pablo Warman, Diana M. Ciaccio, Marta Pena, Gladys Feyling, José García Miras, Mirta Beatriz Rivarola, Marco Aurelio Belgorosky, Alicia Saraco, Nora Isabel |
author2_role |
author author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Aromatase Aromatase Deficiency Founder Effect |
topic |
Aromatase Aromatase Deficiency Founder Effect |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Context: Aromatase is the key enzyme for estrogen biosynthesis and is encoded by the CYP19A1 gene. Since 1991, several molecular CYP19A1 gene alterations associated with aromatase deficiency have been described in both sexes. Objective: The objective of the study was to detect CYP19A1 mutations in five aromatasedeficient 46, XX patients, to describe the clinical follow-up from birth to puberty and to perform haplotype analysis associated with the high-frequency c.628G>A splice mutation in Argentinean patients. Design: The design of the study was the sequencing of the coding and flanking intronic regions of the CYP19A1 gene in all patients and parents. Haplotype analysis of patients carrying the c.628G>A mutation was also performed. Patients: Clinical and biochemical findings in five new cases and one previously reported female aromatase-deficient patient (46, XX) are described. All patients presented with ambiguous genitalia at birth. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency as well as other steroidogenic defects were ruled out. Results: Phenotypic variability among the affected patients was found during follow-up. Direct sequencing of the CYP19A1 gene from genomic DNA revealed one novel mutation (c.574C>T) in two patients. In silico analysis predicted the c.574C>T mutation to be probably damaging. Four of six nonrelated patients presented with the c.628G>A splice mutation. Haplotype analysis showed that the c.628G>A splice mutation is associated with the same haplotype in our population. Conclusions: Increased knowledge on phenotypical variability found in female aromatase-deficient patients is useful to improve the detection rate in this disorder. In our population, a genetic founder defect has probably contributed to an increase in the incidence of the c.628G>A splice mutation. Fil: Marino, Roxana Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Garrido, Natalia Perez. 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: Juanes, Matías Hernan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rocco, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ramirez, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Warman, Diana M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Ciaccio, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Pena, Gladys. Hospital Infantil Municipal de Cordoba; Argentina Fil: Feyling, José García. Hospital Regional de Concepcion; Argentina Fil: Miras, Mirta Beatriz. Hospital de Ninos de la Santisima Trinidad; 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 Fil: Saraco, Nora Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
description |
Context: Aromatase is the key enzyme for estrogen biosynthesis and is encoded by the CYP19A1 gene. Since 1991, several molecular CYP19A1 gene alterations associated with aromatase deficiency have been described in both sexes. Objective: The objective of the study was to detect CYP19A1 mutations in five aromatasedeficient 46, XX patients, to describe the clinical follow-up from birth to puberty and to perform haplotype analysis associated with the high-frequency c.628G>A splice mutation in Argentinean patients. Design: The design of the study was the sequencing of the coding and flanking intronic regions of the CYP19A1 gene in all patients and parents. Haplotype analysis of patients carrying the c.628G>A mutation was also performed. Patients: Clinical and biochemical findings in five new cases and one previously reported female aromatase-deficient patient (46, XX) are described. All patients presented with ambiguous genitalia at birth. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency as well as other steroidogenic defects were ruled out. Results: Phenotypic variability among the affected patients was found during follow-up. Direct sequencing of the CYP19A1 gene from genomic DNA revealed one novel mutation (c.574C>T) in two patients. In silico analysis predicted the c.574C>T mutation to be probably damaging. Four of six nonrelated patients presented with the c.628G>A splice mutation. Haplotype analysis showed that the c.628G>A splice mutation is associated with the same haplotype in our population. Conclusions: Increased knowledge on phenotypical variability found in female aromatase-deficient patients is useful to improve the detection rate in this disorder. In our population, a genetic founder defect has probably contributed to an increase in the incidence of the c.628G>A splice mutation. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-02 |
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/11336/37138 Marino, Roxana Marcela; Garrido, Natalia Perez; Costanzo, Mariana; Guercio, Gabriela Viviana; Juanes, Matías Hernan; et al.; Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 100; 2; 2-2015; E301-E307 0021-972X CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/37138 |
identifier_str_mv |
Marino, Roxana Marcela; Garrido, Natalia Perez; Costanzo, Mariana; Guercio, Gabriela Viviana; Juanes, Matías Hernan; et al.; Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 100; 2; 2-2015; E301-E307 0021-972X CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1210/jc.2014-2967 info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jcem/article/100/2/E301/2814966 |
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 |
dc.publisher.none.fl_str_mv |
Endocrine Society |
publisher.none.fl_str_mv |
Endocrine Society |
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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1844614353254350848 |
score |
13.070432 |