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Article: 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 |
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Authors | Portnoi, 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, PierrePichard, Caroline de MallerayRavel, CeliaChristin-Maitre, SophieBrauner, RajaRossetti, RaffaellaPersani, LucaCharreau, Eduardo H.Dain, LilianaChiauzzi, Violeta A.Mazen, InasRouba, HassanSchluth-Bolard, CarolineMacGowan, StuartMcLean, W. H.IrwinPatin, EtienneMeyts, Ewa Rajpert DeJauch, RalfAchermann, John C.Siffroi, Jean PierreMcElreavey, KenBashamboo, Anu |
Issue Date | 2018 |
Citation | Human Molecular Genetics, 2018, v. 27, n. 7, p. 1228-1240 How to Cite? |
Abstract | © The Author(s) 2018. Published by Oxford University Press. All rights reserved. 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. |
Persistent Identifier | http://hdl.handle.net/10722/253135 |
ISSN | 2021 Impact Factor: 5.121 2020 SCImago Journal Rankings: 2.811 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Portnoi, Marie France | - |
dc.contributor.author | Dumargne, Marie Charlotte | - |
dc.contributor.author | Rojo, Sandra | - |
dc.contributor.author | Witchel, Selma F. | - |
dc.contributor.author | Duncan, Andrew J. | - |
dc.contributor.author | Eozenou, Caroline | - |
dc.contributor.author | Bignon-Topalovic, Joelle | - |
dc.contributor.author | Yatsenko, Svetlana A. | - |
dc.contributor.author | Rajkovic, Aleksandar | - |
dc.contributor.author | Reyes-Mugica, Miguel | - |
dc.contributor.author | Almstrup, Kristian | - |
dc.contributor.author | Fusee, Leila | - |
dc.contributor.author | Srivastava, Yogesh | - |
dc.contributor.author | Chantot-Bastaraud, Sandra | - |
dc.contributor.author | Hyon, Capucine | - |
dc.contributor.author | Louis-Sylvestre, Christine | - |
dc.contributor.author | Validire, Pierre | - |
dc.contributor.author | Pichard, Caroline de Malleray | - |
dc.contributor.author | Ravel, Celia | - |
dc.contributor.author | Christin-Maitre, Sophie | - |
dc.contributor.author | Brauner, Raja | - |
dc.contributor.author | Rossetti, Raffaella | - |
dc.contributor.author | Persani, Luca | - |
dc.contributor.author | Charreau, Eduardo H. | - |
dc.contributor.author | Dain, Liliana | - |
dc.contributor.author | Chiauzzi, Violeta A. | - |
dc.contributor.author | Mazen, Inas | - |
dc.contributor.author | Rouba, Hassan | - |
dc.contributor.author | Schluth-Bolard, Caroline | - |
dc.contributor.author | MacGowan, Stuart | - |
dc.contributor.author | McLean, W. H.Irwin | - |
dc.contributor.author | Patin, Etienne | - |
dc.contributor.author | Meyts, Ewa Rajpert De | - |
dc.contributor.author | Jauch, Ralf | - |
dc.contributor.author | Achermann, John C. | - |
dc.contributor.author | Siffroi, Jean Pierre | - |
dc.contributor.author | McElreavey, Ken | - |
dc.contributor.author | Bashamboo, Anu | - |
dc.date.accessioned | 2018-05-11T05:38:42Z | - |
dc.date.available | 2018-05-11T05:38:42Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Human Molecular Genetics, 2018, v. 27, n. 7, p. 1228-1240 | - |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.uri | http://hdl.handle.net/10722/253135 | - |
dc.description.abstract | © The Author(s) 2018. Published by Oxford University Press. All rights reserved. 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. | - |
dc.language | eng | - |
dc.relation.ispartof | Human Molecular Genetics | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1093/hmg/ddy037 | - |
dc.identifier.scopus | eid_2-s2.0-85044872508 | - |
dc.identifier.volume | 27 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | 1228 | - |
dc.identifier.epage | 1240 | - |
dc.identifier.eissn | 1460-2083 | - |
dc.identifier.isi | WOS:000429009400009 | - |
dc.identifier.f1000 | 732571762 | - |
dc.identifier.issnl | 0964-6906 | - |