دورية أكاديمية
Clinical and genetic characteristics of a large international cohort of individuals with rare NR5A1/SF-1 variants of sex development
| العنوان: | Clinical and genetic characteristics of a large international cohort of individuals with rare NR5A1/SF-1 variants of sex development |
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| المؤلفون: | Kouri, Chrysanthi, Sommer, Grit, Martinez de Lapiscina, Idoia, Elzenaty, Rawda Naamneh, Tack, Lloyd, Cools, Martine, Ahmed, S. Faisal, Flück, Christa E., Abali, Saygin, Abali, Zehra Yavas, Akin, Leyla, Almaraz, Maricruz, Audí, Laura, Aydin, Murat, Balsamo, Antonio, Baronio, Federico, Bryce, Jillian, Busiah, Kanetee, Caimari, Maria, Camats-Tarruella, Núria, Campos-Martorell, Ariadna, Castaño, Luis, Casteràs, Anna, Çetinkaya, Semra, Chan, Yee-Ming, Claahsen-van der Grinten, Hedi L., Costa, Ines, Darendeliler, Fatma Feyza, Davies, Justin H., Esteva, Isabel, Fabbri-Scallet, Helena, Finlayson, Courtney A., Garcia, Emilio, Garcia Cuartero, Beatriz, German, Alina, Globa, Evgenia, Guerra-Junior, Gil, Guerrero, Julio, Guran, Tulay, Hannema, Sabine E., Hiort, Olaf, Hirsch, Josephine, Hughes, Leuan, Janner, Marco, Kolesinska, Zofia, Lachlan, Katherine, Lauber-Biason, Anna, Malikova, Jana Krenek, l'Allemand, Dagmar, Lenhnerr-Taube, Nina, Lucas-Herald, Angela, Mammadova, Jamala, MсElreavey, Kenneth, Mericq, Veronica, Mönig, Isabel, Moreno, Francisca, Mührer, Julia, Niedziela, Marek, Nordenstrom, Anna, Orman, Burçe, Poyrazoglu, Sukran, Rial, Jose M., Rutter, Meilan M., Rodríguez, Amaia, Schafer-Kalkhoff, Tara, Sauter, Kay-Sara, Seneviratne, Sumudu Nimali, Sredkova-Ruskova, Maria, Tadokoro-Cuccaro, Rieko, Thankamony, Ajay, Tomé, Mónica, Vela, Amaia, Wasniewska, Malgorzata, Zangen, David, Zelinska, Nataliya, next study group, SF1 |
| المصدر: | EBIOMEDICINE ; ISSN: 2352-3964 |
| بيانات النشر: | Elsevier BV |
| سنة النشر: | 2024 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, General Biochemistry, Genetics and Molecular Biology, General Medicine, Intersex, Genetics of sex determination and differentiation, Broad phenotype, Differences of sex development (DSD) |
| الوصف: | Background Steroidogenic factor 1 (SF-1/NR5A1) is essential for human sex development. Heterozygous NR5A1/SF-1 variants manifest with a broad range of phenotypes of differences of sex development (DSD), which remain unexplained. Methods We conducted a retrospective analysis on the so far largest international cohort of individuals with NR5A1/ SF -1 variants, identified through the I-DSD registry and a research network. Findings Among 197 individuals with NR5A1/SF-1 variants, we confirmed diverse phenotypes. Over 70% of 46, XY individuals had a severe DSD phenotype, while 90% of 46, XX individuals had female-typical sex development. Close to 100 different novel and known NR5A1/SF-1 variants were identified, without specific hot spots. Additionally, likely disease-associated variants in other genes were reported in 32 individuals out of 128 tested (25%), particularly in those with severe or opposite sex DSD phenotypes. Interestingly, 48% of these variants were found in known DSD or SF -1 interacting genes, but no frequent gene-clusters were identified. Sex registration at birth varied, with <10% undergoing reassignment. Gonadectomy was performed in 30% and genital surgery in 58%. Associated organ anomalies were observed in 27% of individuals with a DSD, mainly concerning the spleen. Intrafamilial phenotypes also varied considerably. Interpretation The observed phenotypic variability in individuals and families with NR5A1/SF-1 variants is large and remains unpredictable. It may often not be solely explained by the monogenic pathogenicity of the NR5A1/SF-1 variants but is likely influenced by additional genetic variants and as -yet -unknown factors. Funding Swiss National Science Foundation (320030-197725) and Boveri Foundation Zurich, Switzerland. Copyright Crown Copyright (c) 2023 Published by Elsevier B.V. This is an open access article under the CC BY -NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0Test/). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/01HNCPZCJZ3KBEFX9FRCPDMBXNTest; http://hdl.handle.net/1854/LU-01HNCPZCJZ3KBEFX9FRCPDMBXNTest; http://doi.org/10.1016/j.ebiom.2023.104941Test; https://biblio.ugent.be/publication/01HNCPZCJZ3KBEFX9FRCPDMBXN/file/01HNCQ3RJ93X17ZM92FF9A279FTest |
| DOI: | 10.1016/j.ebiom.2023.104941 |
| الإتاحة: | https://doi.org/10.1016/j.ebiom.2023.104941Test https://biblio.ugent.be/publication/01HNCPZCJZ3KBEFX9FRCPDMBXNTest http://hdl.handle.net/1854/LU-01HNCPZCJZ3KBEFX9FRCPDMBXNTest https://biblio.ugent.be/publication/01HNCPZCJZ3KBEFX9FRCPDMBXN/file/01HNCQ3RJ93X17ZM92FF9A279FTest |
| حقوق: | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License (CC BY-NC-ND 4.0) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6A7493F6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.ebiom.2023.104941 |
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