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| Verfasst von: | Hoed, Joery den [VerfasserIn]  |
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| | de Boer, Elke [VerfasserIn] |
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| | Voisin, Norine [VerfasserIn] |
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| | Dingemans, Alexander J. M. [VerfasserIn] |
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| | Guex, Nicolas [VerfasserIn] |
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| | Wiel, Laurens [VerfasserIn] |
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| | Nellaker, Christoffer [VerfasserIn] |
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| | Amudhavalli, Shivarajan M. [VerfasserIn] |
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| | Banka, Siddharth [VerfasserIn] |
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| | Bena, Frederique S. [VerfasserIn] |
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| | Ben-Zeev, Bruria [VerfasserIn] |
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| | Bonagura, Vincent R. [VerfasserIn] |
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| | Bruel, Ange-Line [VerfasserIn] |
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| | Brunet, Theresa [VerfasserIn] |
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| | Brunner, Han G. [VerfasserIn] |
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| | Chew, Hui B. [VerfasserIn] |
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| | Chrast, Jacqueline [VerfasserIn] |
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| | Cimbalistienė, Loreta [VerfasserIn] |
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| | Coon, Hilary [VerfasserIn] |
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| | Délot, Emmanuèlle C. [VerfasserIn] |
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| | Démurger, Florence [VerfasserIn] |
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| | Denommé-Pichon, Anne-Sophie [VerfasserIn] |
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| | Depienne, Christel [VerfasserIn] |
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| | Donnai, Dian [VerfasserIn] |
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| | Dyment, David A. [VerfasserIn] |
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| | Elpeleg, Orly [VerfasserIn] |
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| | Faivre, Laurence [VerfasserIn] |
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| | Gilissen, Christian [VerfasserIn] |
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| | Granger, Leslie [VerfasserIn] |
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| | Haber, Benjamin [VerfasserIn] |
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| | Hachiya, Yasuo [VerfasserIn] |
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| | Abedi, Yasmin Hamzavi [VerfasserIn] |
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| | Hanebeck, Jennifer [VerfasserIn] |
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| | Hehir-Kwa, Jayne Y. [VerfasserIn] |
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| | Horist, Brooke [VerfasserIn] |
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| | Itai, Toshiyuki [VerfasserIn] |
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| | Kotzaeridou, Urania [VerfasserIn] |
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| | Orec, Laura [VerfasserIn] |
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| Titel: | Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction |
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| Verf.angabe: | Joery den Hoed, Elke de Boer, Norine Voisin, Alexander J.M. Dingemans, Nicolas Guex, Laurens Wiel, Christoffer Nellaker, Shivarajan M. Amudhavalli, Siddharth Banka, Frederique S. Bena, Bruria Ben-Zeev, Vincent R. Bonagura, Ange-Line Bruel, Theresa Brunet, Han G. Brunner, Hui B. Chew, Jacqueline Chrast, Loreta Cimbalistienė, Hilary Coon, Emmanuèlle C. Délot, Florence Démurger, Anne-Sophie Denommé-Pichon, Christel Depienne, Dian Donnai, David A. Dyment, Orly Elpeleg, Laurence Faivre, Christian Gilissen, Leslie Granger, Benjamin Haber, Yasuo Hachiya, Yasmin Hamzavi Abedi, Jennifer Hanebeck, Jayne Y. Hehir-Kwa, Brooke Horist, Toshiyuki Itai, Adam Jackson, Rosalyn Jewell, Kelly L. Jones, Shelagh Joss, Hirofumi Kashii, Mitsuhiro Kato, Anja A. Kattentidt-Mouravieva, Fernando Kok, Urania Kotzaeridou, Vidya Krishnamurthy, Vaidutis Kučinskas, Alma Kuechler, Alinoë Lavillaureix, Pengfei Liu, Linda Manwaring, Naomichi Matsumoto, Benoît Mazel, Kirsty McWalter, Vardiella Meiner, Mohamad A. Mikati, Satoko Miyatake, Takeshi Mizuguchi, Lip H. Moey, Shehla Mohammed, Hagar Mor-Shaked, Hayley Mountford, Ruth Newbury-Ecob, Sylvie Odent, Laura Orec, Matthew Osmond, Timothy B. Palculict, Michael Parker, Andrea K. Petersen, Rolph Pfundt, Eglė Preikšaitienė, Kelly Radtke, Emmanuelle Ranza, Jill A. Rosenfeld, Teresa Santiago-Sim, Caitlin Schwager, Margje Sinnema, Lot Snijders Blok, Rebecca C. Spillmann, Alexander P.A. Stegmann, Isabelle Thiffault, Linh Tran, Adi Vaknin-Dembinsky, Juliana H. Vedovato-dos-Santos, Samantha A. Schrier Vergano, Eric Vilain, Antonio Vitobello, Matias Wagner, Androu Waheeb, Marcia Willing, Britton Zuccarelli, Usha Kini, Dianne F. Newbury, Tjitske Kleefstra, Alexandre Reymond, Simon E. Fisher, Lisenka E.L.M. Vissers |
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| E-Jahr: | 2021 |
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| Jahr: | 28 January 2021 |
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| Umfang: | 11 S. |
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| Teil: | volume:108 |
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| | year:2021 |
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| | number:2 |
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| | month:02 |
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| | pages:346-356 |
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| | extent:11 |
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| Fussnoten: | Gesehen am 24.07.2021 |
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| Titel Quelle: | Enthalten in: The American journal of human genetics |
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| Ort Quelle: | New York, NY [u.a.] : Cell Press, 1949 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 108(2021), 2 vom: Feb., Seite 346-356 |
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| ISSN Quelle: | 1537-6605 |
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| Abstract: | Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability. |
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| DOI: | doi:10.1016/j.ajhg.2021.01.007 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1016/j.ajhg.2021.01.007 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S0002929721000070 |
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| | DOI: https://doi.org/10.1016/j.ajhg.2021.01.007 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | cell-based functional assays |
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| | de novo variants |
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| | HPO-based analysis |
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| | intellectual disability |
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| | neurodevelopmental disorders |
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| | SATB1 |
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| | seizures |
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| | teeth abnormalities |
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| K10plus-PPN: | 1764273338 |
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| Verknüpfungen: | → Zeitschrift |
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Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction / Hoed, Joery den [VerfasserIn]; 28 January 2021 (Online-Ressource)
