An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues
- Autores
- Saraco, Nora Isabel; Nesi Franca, Suzana; Sainz, Romina Belén; Marino, Roxana Marcela; Marques Pereira, Rosana; La Pastina, Julia; Perez Garrido, Natalia; Sandrini, Romolo; Rivarola, Marco Aurelio; Lacerda, Luiz de; Belgorosky, Alicia
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background/Aims: Splicing CYP19 gene variants causingaromatase deficiency in 46,XX disorder of sexual development(DSD) patients have been reported in a few cases. Amisbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast developmentbut an incomplete sex maturation progress. Theaim of this study was to functionally characterize a novelCYP19A1 intronic homozygote mutation (IVS9+5G>A) in a46,XX DSD girl presenting spontaneous breast developmentand primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Methods:Genomic DNA analysis, splicing prediction programs,splicing assays, and in vitro protein expression and enzymeactivity analyses were carried out. CYP19A1 mRNA expressionin human steroidogenic tissues was also studied. Results:A novel IVS9+5G>A homozygote mutation was found.In silico analysis predicts the disappearance of the splicingdonor site in intron 9, confirmed by patient peripheral leukocytecP450arom and in vitro studies. Protein analysisshowed a shorter and inactive protein. The intron 9 transcriptvariant was also found in human steroidogenic tissues.Conclusions: The mutation IVS9+5G>A generates a splicingvariant that includes intron 9 which is also present in normalhuman steroidogenic tissues, suggesting that a misbalancebetween normal and aberrant splicing variants might occurin target tissues, explaining the clinical phenotype in the affectedpatient.
Fil: Saraco, Nora Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nesi Franca, Suzana. Universidade Federal do Paraná; Brasil
Fil: Sainz, Romina Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Marino, Roxana Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Marques Pereira, Rosana. Universidade Federal do Paraná; Brasil
Fil: La Pastina, Julia. Universidade Federal do Paraná; Brasil
Fil: Perez Garrido, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Sandrini, Romolo. Universidade Federal do Paraná; Brasil
Fil: Rivarola, Marco Aurelio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Lacerda, Luiz de. Universidade Federal do Paraná; Brasil
Fil: Belgorosky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina - Materia
-
Aromatase Deficiency
Mutation
Cyp19a1
Steroidogenic Tissues
Splicing - 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:11336/41793
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oai:ri.conicet.gov.ar:11336/41793 |
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3498 |
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CONICET Digital (CONICET) |
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An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic TissuesSaraco, Nora IsabelNesi Franca, SuzanaSainz, Romina BelénMarino, Roxana MarcelaMarques Pereira, RosanaLa Pastina, JuliaPerez Garrido, NataliaSandrini, RomoloRivarola, Marco AurelioLacerda, Luiz deBelgorosky, AliciaAromatase DeficiencyMutationCyp19a1Steroidogenic TissuesSplicinghttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background/Aims: Splicing CYP19 gene variants causingaromatase deficiency in 46,XX disorder of sexual development(DSD) patients have been reported in a few cases. Amisbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast developmentbut an incomplete sex maturation progress. Theaim of this study was to functionally characterize a novelCYP19A1 intronic homozygote mutation (IVS9+5G>A) in a46,XX DSD girl presenting spontaneous breast developmentand primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Methods:Genomic DNA analysis, splicing prediction programs,splicing assays, and in vitro protein expression and enzymeactivity analyses were carried out. CYP19A1 mRNA expressionin human steroidogenic tissues was also studied. Results:A novel IVS9+5G>A homozygote mutation was found.In silico analysis predicts the disappearance of the splicingdonor site in intron 9, confirmed by patient peripheral leukocytecP450arom and in vitro studies. Protein analysisshowed a shorter and inactive protein. The intron 9 transcriptvariant was also found in human steroidogenic tissues.Conclusions: The mutation IVS9+5G>A generates a splicingvariant that includes intron 9 which is also present in normalhuman steroidogenic tissues, suggesting that a misbalancebetween normal and aberrant splicing variants might occurin target tissues, explaining the clinical phenotype in the affectedpatient.Fil: Saraco, Nora Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nesi Franca, Suzana. Universidade Federal do Paraná; BrasilFil: Sainz, Romina Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Marino, Roxana Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Marques Pereira, Rosana. Universidade Federal do Paraná; BrasilFil: La Pastina, Julia. Universidade Federal do Paraná; BrasilFil: Perez Garrido, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Sandrini, Romolo. Universidade Federal do Paraná; BrasilFil: Rivarola, Marco Aurelio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Lacerda, Luiz de. Universidade Federal do Paraná; BrasilFil: Belgorosky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaKarger2015-08info: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/11336/41793Saraco, Nora Isabel; Nesi Franca, Suzana; Sainz, Romina Belén; Marino, Roxana Marcela; Marques Pereira, Rosana; et al.; An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues; Karger; Hormone Research in Paediatrics; 84; 4; 8-2015; 275-2821663-2826CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1159/000437142info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/437142info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:26Zoai:ri.conicet.gov.ar:11336/41793instacron: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 09:33:26.457CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues |
title |
An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues |
spellingShingle |
An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues Saraco, Nora Isabel Aromatase Deficiency Mutation Cyp19a1 Steroidogenic Tissues Splicing |
title_short |
An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues |
title_full |
An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues |
title_fullStr |
An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues |
title_full_unstemmed |
An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues |
title_sort |
An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues |
dc.creator.none.fl_str_mv |
Saraco, Nora Isabel Nesi Franca, Suzana Sainz, Romina Belén Marino, Roxana Marcela Marques Pereira, Rosana La Pastina, Julia Perez Garrido, Natalia Sandrini, Romolo Rivarola, Marco Aurelio Lacerda, Luiz de Belgorosky, Alicia |
author |
Saraco, Nora Isabel |
author_facet |
Saraco, Nora Isabel Nesi Franca, Suzana Sainz, Romina Belén Marino, Roxana Marcela Marques Pereira, Rosana La Pastina, Julia Perez Garrido, Natalia Sandrini, Romolo Rivarola, Marco Aurelio Lacerda, Luiz de Belgorosky, Alicia |
author_role |
author |
author2 |
Nesi Franca, Suzana Sainz, Romina Belén Marino, Roxana Marcela Marques Pereira, Rosana La Pastina, Julia Perez Garrido, Natalia Sandrini, Romolo Rivarola, Marco Aurelio Lacerda, Luiz de Belgorosky, Alicia |
author2_role |
author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Aromatase Deficiency Mutation Cyp19a1 Steroidogenic Tissues Splicing |
topic |
Aromatase Deficiency Mutation Cyp19a1 Steroidogenic Tissues Splicing |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Background/Aims: Splicing CYP19 gene variants causingaromatase deficiency in 46,XX disorder of sexual development(DSD) patients have been reported in a few cases. Amisbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast developmentbut an incomplete sex maturation progress. Theaim of this study was to functionally characterize a novelCYP19A1 intronic homozygote mutation (IVS9+5G>A) in a46,XX DSD girl presenting spontaneous breast developmentand primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Methods:Genomic DNA analysis, splicing prediction programs,splicing assays, and in vitro protein expression and enzymeactivity analyses were carried out. CYP19A1 mRNA expressionin human steroidogenic tissues was also studied. Results:A novel IVS9+5G>A homozygote mutation was found.In silico analysis predicts the disappearance of the splicingdonor site in intron 9, confirmed by patient peripheral leukocytecP450arom and in vitro studies. Protein analysisshowed a shorter and inactive protein. The intron 9 transcriptvariant was also found in human steroidogenic tissues.Conclusions: The mutation IVS9+5G>A generates a splicingvariant that includes intron 9 which is also present in normalhuman steroidogenic tissues, suggesting that a misbalancebetween normal and aberrant splicing variants might occurin target tissues, explaining the clinical phenotype in the affectedpatient. Fil: Saraco, Nora Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Nesi Franca, Suzana. Universidade Federal do Paraná; Brasil Fil: Sainz, Romina Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina Fil: Marino, Roxana Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina Fil: Marques Pereira, Rosana. Universidade Federal do Paraná; Brasil Fil: La Pastina, Julia. Universidade Federal do Paraná; Brasil Fil: Perez Garrido, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina Fil: Sandrini, Romolo. Universidade Federal do Paraná; Brasil Fil: Rivarola, Marco Aurelio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina Fil: Lacerda, Luiz de. Universidade Federal do Paraná; Brasil Fil: Belgorosky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina |
description |
Background/Aims: Splicing CYP19 gene variants causingaromatase deficiency in 46,XX disorder of sexual development(DSD) patients have been reported in a few cases. Amisbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast developmentbut an incomplete sex maturation progress. Theaim of this study was to functionally characterize a novelCYP19A1 intronic homozygote mutation (IVS9+5G>A) in a46,XX DSD girl presenting spontaneous breast developmentand primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Methods:Genomic DNA analysis, splicing prediction programs,splicing assays, and in vitro protein expression and enzymeactivity analyses were carried out. CYP19A1 mRNA expressionin human steroidogenic tissues was also studied. Results:A novel IVS9+5G>A homozygote mutation was found.In silico analysis predicts the disappearance of the splicingdonor site in intron 9, confirmed by patient peripheral leukocytecP450arom and in vitro studies. Protein analysisshowed a shorter and inactive protein. The intron 9 transcriptvariant was also found in human steroidogenic tissues.Conclusions: The mutation IVS9+5G>A generates a splicingvariant that includes intron 9 which is also present in normalhuman steroidogenic tissues, suggesting that a misbalancebetween normal and aberrant splicing variants might occurin target tissues, explaining the clinical phenotype in the affectedpatient. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-08 |
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/11336/41793 Saraco, Nora Isabel; Nesi Franca, Suzana; Sainz, Romina Belén; Marino, Roxana Marcela; Marques Pereira, Rosana; et al.; An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues; Karger; Hormone Research in Paediatrics; 84; 4; 8-2015; 275-282 1663-2826 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/41793 |
identifier_str_mv |
Saraco, Nora Isabel; Nesi Franca, Suzana; Sainz, Romina Belén; Marino, Roxana Marcela; Marques Pereira, Rosana; et al.; An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues; Karger; Hormone Research in Paediatrics; 84; 4; 8-2015; 275-282 1663-2826 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1159/000437142 info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/437142 |
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 |
Karger |
publisher.none.fl_str_mv |
Karger |
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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1844613026987114496 |
score |
13.070432 |