دورية أكاديمية
Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome
| العنوان: | Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome |
|---|---|
| المؤلفون: | Weerts, Marjolein J.A., Lanko, Kristina, Guzmán-Vega, Francisco J., Jackson, Adam, Ramakrishnan, Reshmi, Cardona-Londoño, Kelly J., Peña-Guerra, Karla A., van Bever, Yolande, van Paassen, Barbara W., Kievit, Anneke, van Slegtenhorst, Marjon, Allen, Nicholas M., Kehoe, Caroline M., Robinson, Hannah K., Pang, Lewis, Banu, Selina H., Zaman, Mashaya, Efthymiou, Stephanie, Houlden, Henry, Järvelä, Irma, Lauronen, Leena, Määttä, Tuomo, Schrauwen, Isabelle, Leal, Suzanne M., Ruivenkamp, Claudia A.L., Barge-Schaapveld, Daniela Q.C.M., Peeters-Scholte, Cacha M.P.C.D., Galehdari, Hamid, Mazaheri, Neda, Sisodiya, Sanjay M., Harrison, Victoria, Sun, Angela, Thies, Jenny, Pedroza, Luis Alberto, Lara-Taranchenko, Yana, Chinn, Ivan K., Lupski, James R., Garza-Flores, Alexandra, McGlothlin, Jeffery, Yang, Lin, Huang, Shaoping, Wang, Xiaodong, Jewett, Tamison, Rosso, Gretchen, Lin, Xi, Mohammed, Shehla, Merritt, J. Lawrence, II., Mirzaa, Ghayda M., Timms, Andrew E., Scheck, Joshua, Elting, Mariet W., Polstra, Abeltje M., Schenck, Lauren, Ruzhnikov, Maura R.Z., Vetro, Annalisa, Montomoli, Martino, Guerrini, Renzo, Koboldt, Daniel C., Mihalic Mosher, Theresa, Pastore, Matthew T., McBride, Kim L., Peng, Jing, Pan, Zou, Willemsen, Marjolein, Koning, Susanne, Turnpenny, Peter D., de Vries, Bert B.A., Gilissen, Christian, Pfundt, Rolph, Lees, Melissa, Braddock, Stephen R., Klemp, Kara C., Vansenne, Fleur, van Gijn, Marielle E., Quindipan, Catherine, Deardorff, Matthew A., Hamm, J. Austin, Putnam, Abbey M., Baud, Rebecca, Walsh, Laurence, Lynch, Sally A., Baptista, Julia, Person, Richard E., Monaghan, Kristin G., Crunk, Amy, Keller-Ramey, Jennifer, Reich, Adi, Elloumi, Houda Zghal, Alders, Marielle, Kerkhof, Jennifer, McConkey, Haley, Haghshenas, Sadegheh, Maroofian, Reza, Sadikovic, Bekim, Banka, Siddharth, Arold, Stefan T., Barakat, Tahsin Stefan |
| المساهمون: | Medical and Molecular Genetics, School of Medicine |
| المصدر: | PMC |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2021 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | Epilepsy, Histone-Lysine N-Methyltransferase, Intellectual disability, Neurodevelopmental disorders, Seizures |
| الوصف: | Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Genetics in Medicine; Weerts MJA, Lanko K, Guzmán-Vega FJ, et al. Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome. Genet Med. 2021;23(11):2122-2137. doi:10.1038/s41436-021-01246-2; https://hdl.handle.net/1805/31993Test |
| الإتاحة: | https://doi.org/10.1038/s41436-021-01246-2Test https://hdl.handle.net/1805/31993Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.B216DAC3 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |