Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies
- Autores
- Portnoi, Marie France; Dumargne, Marie Charlotte; Rojo, Sandra; Witchel, Selma F.; Duncan, Andrew J.; Eozenou, Caroline; Bignon Topalovic, Joelle; Yatsenko, Svetlana A.; Rajkovic, Aleksandar; Reyes Mugica, Miguel; Almstrup, Kristian; Fusee, Leila; Srivastava, Yogesh; Chantot Bastaraud, Sandra; Hyon, Capucine; Louis Sylvestre, Christine; Validire, Pierre; de Malleray Pichard, Caroline; Ravel, Celia; Christin Maitre, Sophie; Brauner, Raja; Rossetti, Raffaella; Persani, Luca; Charreau, Eduardo Hernan; Dain, Liliana Beatriz; Chiauzzi, Violeta Alicia; Mazen, Inas; Rouba, Hassan; Schluth Bolard, Caroline; Mac Gowan, Stuart; Mc Lean, W. H. Irwin; Patin, Etienne; Rajpert De Meyts, Ewa; Jauch, Ralf; Achermann, John C.; Siffroi, Jean Pierre; Mc Elreavey, Ken; Bashamboo, Anu
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n=274) and two independent cohorts of women with primary ovarian insufficiency (POI; n=153 and n=104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P=4.5×10-5) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI.
Fil: Portnoi, Marie France. Inserm; Francia. Sorbonne Université. Faculté de Medecine; Francia. Hôpital Armand Trousseau; Francia
Fil: Dumargne, Marie Charlotte. Instituto Pasteur; Francia
Fil: Rojo, Sandra. Instituto Pasteur; Francia
Fil: Witchel, Selma F.. University of Pittsburgh; Estados Unidos
Fil: Duncan, Andrew J.. Great Ormond Street Hospital for Children; Reino Unido
Fil: Eozenou, Caroline. Instituto Pasteur; Francia
Fil: Bignon Topalovic, Joelle. Instituto Pasteur; Francia
Fil: Yatsenko, Svetlana A.. University of Pittsburgh; Estados Unidos
Fil: Rajkovic, Aleksandar. University of Pittsburgh; Estados Unidos
Fil: Reyes Mugica, Miguel. University of Pittsburgh; Estados Unidos
Fil: Almstrup, Kristian. Rigshospitalet; Dinamarca
Fil: Fusee, Leila. Instituto Pasteur; Francia
Fil: Srivastava, Yogesh. Chinese Academy of Sciences; República de China
Fil: Chantot Bastaraud, Sandra. Hôpital Armand Trousseau; Francia
Fil: Hyon, Capucine. Hôpital Armand Trousseau; Francia. Inserm; Francia
Fil: Louis Sylvestre, Christine. Institut Mutualiste Montsouris; Francia
Fil: Validire, Pierre. Institut Mutualiste Montsouris; Francia
Fil: de Malleray Pichard, Caroline. Hôpital Cochin; Francia
Fil: Ravel, Celia. Centre Hospitalier Universitaire de Rennes; Francia
Fil: Christin Maitre, Sophie. Inserm; Francia. Hôpital Saint-Antoine; Francia
Fil: Brauner, Raja. Universite de Paris; Francia
Fil: Rossetti, Raffaella. Università degli Studi di Milano; Italia. Istituto Auxologico Italiano; Italia
Fil: Persani, Luca. Istituto Auxologico Italiano; Italia. Università degli Studi di Milano; Italia
Fil: Charreau, Eduardo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; Argentina
Fil: Dain, Liliana Beatriz. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Chiauzzi, Violeta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; Argentina
Fil: Mazen, Inas. National Research Centre ; Egipto
Fil: Rouba, Hassan. Institut Pasteur du Maroc; Marruecos
Fil: Schluth Bolard, Caroline. Hôpital Femme Mère Enfant; Francia
Fil: Mac Gowan, Stuart. University of Dundee; Reino Unido
Fil: Mc Lean, W. H. Irwin. University of Dundee; Reino Unido
Fil: Patin, Etienne. Instituto Pasteur; Francia
Fil: Rajpert De Meyts, Ewa. Rigshospitalet; Dinamarca
Fil: Jauch, Ralf. Chinese Academy of Sciences; República de China
Fil: Achermann, John C.. Great Ormond Street Hospital for Children; Reino Unido
Fil: Siffroi, Jean Pierre. Hôpital Armand Trousseau; Francia
Fil: Mc Elreavey, Ken. Instituto Pasteur; Francia
Fil: Bashamboo, Anu. Inserm; Francia. Instituto Pasteur; Francia - Materia
-
SOX8
SRY
INFERTILITY
DISORDER OF SEX DEVELOPMENT
MUTATION
OLIGOSPERMIA - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/110617
Ver los metadatos del registro completo
| id |
CONICETDig_d55ac5ee4867bfc9d92d299fa3cd3266 |
|---|---|
| oai_identifier_str |
oai:ri.conicet.gov.ar:11336/110617 |
| network_acronym_str |
CONICETDig |
| repository_id_str |
3498 |
| network_name_str |
CONICET Digital (CONICET) |
| spelling |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomaliesPortnoi, Marie FranceDumargne, Marie CharlotteRojo, SandraWitchel, Selma F.Duncan, Andrew J.Eozenou, CarolineBignon Topalovic, JoelleYatsenko, Svetlana A.Rajkovic, AleksandarReyes Mugica, MiguelAlmstrup, KristianFusee, LeilaSrivastava, YogeshChantot Bastaraud, SandraHyon, CapucineLouis Sylvestre, ChristineValidire, Pierrede Malleray Pichard, CarolineRavel, CeliaChristin Maitre, SophieBrauner, RajaRossetti, RaffaellaPersani, LucaCharreau, Eduardo HernanDain, Liliana BeatrizChiauzzi, Violeta AliciaMazen, InasRouba, HassanSchluth Bolard, CarolineMac Gowan, StuartMc Lean, W. H. IrwinPatin, EtienneRajpert De Meyts, EwaJauch, RalfAchermann, John C.Siffroi, Jean PierreMc Elreavey, KenBashamboo, AnuSOX8SRYINFERTILITYDISORDER OF SEX DEVELOPMENTMUTATIONOLIGOSPERMIAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n=274) and two independent cohorts of women with primary ovarian insufficiency (POI; n=153 and n=104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P=4.5×10-5) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI.Fil: Portnoi, Marie France. Inserm; Francia. Sorbonne Université. Faculté de Medecine; Francia. Hôpital Armand Trousseau; FranciaFil: Dumargne, Marie Charlotte. Instituto Pasteur; FranciaFil: Rojo, Sandra. Instituto Pasteur; FranciaFil: Witchel, Selma F.. University of Pittsburgh; Estados UnidosFil: Duncan, Andrew J.. Great Ormond Street Hospital for Children; Reino UnidoFil: Eozenou, Caroline. Instituto Pasteur; FranciaFil: Bignon Topalovic, Joelle. Instituto Pasteur; FranciaFil: Yatsenko, Svetlana A.. University of Pittsburgh; Estados UnidosFil: Rajkovic, Aleksandar. University of Pittsburgh; Estados UnidosFil: Reyes Mugica, Miguel. University of Pittsburgh; Estados UnidosFil: Almstrup, Kristian. Rigshospitalet; DinamarcaFil: Fusee, Leila. Instituto Pasteur; FranciaFil: Srivastava, Yogesh. Chinese Academy of Sciences; República de ChinaFil: Chantot Bastaraud, Sandra. Hôpital Armand Trousseau; FranciaFil: Hyon, Capucine. Hôpital Armand Trousseau; Francia. Inserm; FranciaFil: Louis Sylvestre, Christine. Institut Mutualiste Montsouris; FranciaFil: Validire, Pierre. Institut Mutualiste Montsouris; FranciaFil: de Malleray Pichard, Caroline. Hôpital Cochin; FranciaFil: Ravel, Celia. Centre Hospitalier Universitaire de Rennes; FranciaFil: Christin Maitre, Sophie. Inserm; Francia. Hôpital Saint-Antoine; FranciaFil: Brauner, Raja. Universite de Paris; FranciaFil: Rossetti, Raffaella. Università degli Studi di Milano; Italia. Istituto Auxologico Italiano; ItaliaFil: Persani, Luca. Istituto Auxologico Italiano; Italia. Università degli Studi di Milano; ItaliaFil: Charreau, Eduardo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; ArgentinaFil: Dain, Liliana Beatriz. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Chiauzzi, Violeta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; ArgentinaFil: Mazen, Inas. National Research Centre ; EgiptoFil: Rouba, Hassan. Institut Pasteur du Maroc; MarruecosFil: Schluth Bolard, Caroline. Hôpital Femme Mère Enfant; FranciaFil: Mac Gowan, Stuart. University of Dundee; Reino UnidoFil: Mc Lean, W. H. Irwin. University of Dundee; Reino UnidoFil: Patin, Etienne. Instituto Pasteur; FranciaFil: Rajpert De Meyts, Ewa. Rigshospitalet; DinamarcaFil: Jauch, Ralf. Chinese Academy of Sciences; República de ChinaFil: Achermann, John C.. Great Ormond Street Hospital for Children; Reino UnidoFil: Siffroi, Jean Pierre. Hôpital Armand Trousseau; FranciaFil: Mc Elreavey, Ken. Instituto Pasteur; FranciaFil: Bashamboo, Anu. Inserm; Francia. Instituto Pasteur; FranciaOxford University Press2018-04info: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/11336/110617Portnoi, Marie France; Dumargne, Marie Charlotte; Rojo, Sandra; Witchel, Selma F.; Duncan, Andrew J.; et al.; Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies; Oxford University Press; Human Molecular Genetics; 27; 7; 4-2018; 1228-12400964-69061460-2083CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/hmg/article/27/7/1228/4823478info:eu-repo/semantics/altIdentifier/doi/10.1093/hmg/ddy037info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:00Zoai:ri.conicet.gov.ar:11336/110617instacron: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 09:39:01.219CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies |
| title |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies |
| spellingShingle |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies Portnoi, Marie France SOX8 SRY INFERTILITY DISORDER OF SEX DEVELOPMENT MUTATION OLIGOSPERMIA |
| title_short |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies |
| title_full |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies |
| title_fullStr |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies |
| title_full_unstemmed |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies |
| title_sort |
Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies |
| dc.creator.none.fl_str_mv |
Portnoi, Marie France Dumargne, Marie Charlotte Rojo, Sandra Witchel, Selma F. Duncan, Andrew J. Eozenou, Caroline Bignon Topalovic, Joelle Yatsenko, Svetlana A. Rajkovic, Aleksandar Reyes Mugica, Miguel Almstrup, Kristian Fusee, Leila Srivastava, Yogesh Chantot Bastaraud, Sandra Hyon, Capucine Louis Sylvestre, Christine Validire, Pierre de Malleray Pichard, Caroline Ravel, Celia Christin Maitre, Sophie Brauner, Raja Rossetti, Raffaella Persani, Luca Charreau, Eduardo Hernan Dain, Liliana Beatriz Chiauzzi, Violeta Alicia Mazen, Inas Rouba, Hassan Schluth Bolard, Caroline Mac Gowan, Stuart Mc Lean, W. H. Irwin Patin, Etienne Rajpert De Meyts, Ewa Jauch, Ralf Achermann, John C. Siffroi, Jean Pierre Mc Elreavey, Ken Bashamboo, Anu |
| author |
Portnoi, Marie France |
| author_facet |
Portnoi, Marie France Dumargne, Marie Charlotte Rojo, Sandra Witchel, Selma F. Duncan, Andrew J. Eozenou, Caroline Bignon Topalovic, Joelle Yatsenko, Svetlana A. Rajkovic, Aleksandar Reyes Mugica, Miguel Almstrup, Kristian Fusee, Leila Srivastava, Yogesh Chantot Bastaraud, Sandra Hyon, Capucine Louis Sylvestre, Christine Validire, Pierre de Malleray Pichard, Caroline Ravel, Celia Christin Maitre, Sophie Brauner, Raja Rossetti, Raffaella Persani, Luca Charreau, Eduardo Hernan Dain, Liliana Beatriz Chiauzzi, Violeta Alicia Mazen, Inas Rouba, Hassan Schluth Bolard, Caroline Mac Gowan, Stuart Mc Lean, W. H. Irwin Patin, Etienne Rajpert De Meyts, Ewa Jauch, Ralf Achermann, John C. Siffroi, Jean Pierre Mc Elreavey, Ken Bashamboo, Anu |
| author_role |
author |
| author2 |
Dumargne, Marie Charlotte Rojo, Sandra Witchel, Selma F. Duncan, Andrew J. Eozenou, Caroline Bignon Topalovic, Joelle Yatsenko, Svetlana A. Rajkovic, Aleksandar Reyes Mugica, Miguel Almstrup, Kristian Fusee, Leila Srivastava, Yogesh Chantot Bastaraud, Sandra Hyon, Capucine Louis Sylvestre, Christine Validire, Pierre de Malleray Pichard, Caroline Ravel, Celia Christin Maitre, Sophie Brauner, Raja Rossetti, Raffaella Persani, Luca Charreau, Eduardo Hernan Dain, Liliana Beatriz Chiauzzi, Violeta Alicia Mazen, Inas Rouba, Hassan Schluth Bolard, Caroline Mac Gowan, Stuart Mc Lean, W. H. Irwin Patin, Etienne Rajpert De Meyts, Ewa Jauch, Ralf Achermann, John C. Siffroi, Jean Pierre Mc Elreavey, Ken Bashamboo, Anu |
| author2_role |
author author author author author author author author author author author author author author author author author 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 |
SOX8 SRY INFERTILITY DISORDER OF SEX DEVELOPMENT MUTATION OLIGOSPERMIA |
| topic |
SOX8 SRY INFERTILITY DISORDER OF SEX DEVELOPMENT MUTATION OLIGOSPERMIA |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n=274) and two independent cohorts of women with primary ovarian insufficiency (POI; n=153 and n=104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P=4.5×10-5) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI. Fil: Portnoi, Marie France. Inserm; Francia. Sorbonne Université. Faculté de Medecine; Francia. Hôpital Armand Trousseau; Francia Fil: Dumargne, Marie Charlotte. Instituto Pasteur; Francia Fil: Rojo, Sandra. Instituto Pasteur; Francia Fil: Witchel, Selma F.. University of Pittsburgh; Estados Unidos Fil: Duncan, Andrew J.. Great Ormond Street Hospital for Children; Reino Unido Fil: Eozenou, Caroline. Instituto Pasteur; Francia Fil: Bignon Topalovic, Joelle. Instituto Pasteur; Francia Fil: Yatsenko, Svetlana A.. University of Pittsburgh; Estados Unidos Fil: Rajkovic, Aleksandar. University of Pittsburgh; Estados Unidos Fil: Reyes Mugica, Miguel. University of Pittsburgh; Estados Unidos Fil: Almstrup, Kristian. Rigshospitalet; Dinamarca Fil: Fusee, Leila. Instituto Pasteur; Francia Fil: Srivastava, Yogesh. Chinese Academy of Sciences; República de China Fil: Chantot Bastaraud, Sandra. Hôpital Armand Trousseau; Francia Fil: Hyon, Capucine. Hôpital Armand Trousseau; Francia. Inserm; Francia Fil: Louis Sylvestre, Christine. Institut Mutualiste Montsouris; Francia Fil: Validire, Pierre. Institut Mutualiste Montsouris; Francia Fil: de Malleray Pichard, Caroline. Hôpital Cochin; Francia Fil: Ravel, Celia. Centre Hospitalier Universitaire de Rennes; Francia Fil: Christin Maitre, Sophie. Inserm; Francia. Hôpital Saint-Antoine; Francia Fil: Brauner, Raja. Universite de Paris; Francia Fil: Rossetti, Raffaella. Università degli Studi di Milano; Italia. Istituto Auxologico Italiano; Italia Fil: Persani, Luca. Istituto Auxologico Italiano; Italia. Università degli Studi di Milano; Italia Fil: Charreau, Eduardo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; Argentina Fil: Dain, Liliana Beatriz. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Chiauzzi, Violeta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Epidemiologia. Departamento de Investigacion.; Argentina Fil: Mazen, Inas. National Research Centre ; Egipto Fil: Rouba, Hassan. Institut Pasteur du Maroc; Marruecos Fil: Schluth Bolard, Caroline. Hôpital Femme Mère Enfant; Francia Fil: Mac Gowan, Stuart. University of Dundee; Reino Unido Fil: Mc Lean, W. H. Irwin. University of Dundee; Reino Unido Fil: Patin, Etienne. Instituto Pasteur; Francia Fil: Rajpert De Meyts, Ewa. Rigshospitalet; Dinamarca Fil: Jauch, Ralf. Chinese Academy of Sciences; República de China Fil: Achermann, John C.. Great Ormond Street Hospital for Children; Reino Unido Fil: Siffroi, Jean Pierre. Hôpital Armand Trousseau; Francia Fil: Mc Elreavey, Ken. Instituto Pasteur; Francia Fil: Bashamboo, Anu. Inserm; Francia. Instituto Pasteur; Francia |
| description |
SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n=274) and two independent cohorts of women with primary ovarian insufficiency (POI; n=153 and n=104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P=4.5×10-5) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-04 |
| 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/11336/110617 Portnoi, Marie France; Dumargne, Marie Charlotte; Rojo, Sandra; Witchel, Selma F.; Duncan, Andrew J.; et al.; Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies; Oxford University Press; Human Molecular Genetics; 27; 7; 4-2018; 1228-1240 0964-6906 1460-2083 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/110617 |
| identifier_str_mv |
Portnoi, Marie France; Dumargne, Marie Charlotte; Rojo, Sandra; Witchel, Selma F.; Duncan, Andrew J.; et al.; Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies; Oxford University Press; Human Molecular Genetics; 27; 7; 4-2018; 1228-1240 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/article/27/7/1228/4823478 info:eu-repo/semantics/altIdentifier/doi/10.1093/hmg/ddy037 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by/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 |
| 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 |
| _version_ |
1844613233724358656 |
| score |
13.070432 |