دورية أكاديمية
GATAD2B-associated neurodevelopmental disorder (GAND) : clinical and molecular insights into a NuRD-related disorder
| العنوان: | GATAD2B-associated neurodevelopmental disorder (GAND) : clinical and molecular insights into a NuRD-related disorder |
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| المؤلفون: | Shieh, Christine, Jones, Natasha, Vanle, Brigitte, Au, Margaret, Huang, Alden Y, Silva, Ana P G, Lee, Hane, Douine, Emilie D, Otero, Maria G, Choi, Andrew, Grand, Katheryn, Taff, Ingrid P, Delgado, Mauricio R, Hajianpour, M J, Seeley, Andrea, Rohena, Luis, Vernon, Hilary, Gripp, Karen W, Vergano, Samantha A, Mahida, Sonal, Naidu, Sakkubai, Sousa, Ana Berta, Wain, Karen E, Challman, Thomas D, Beek, Geoffrey, Basel, Donald, Ranells, Judith, Smith, Rosemarie, Yusupov, Roman, Freckmann, Mary-Louise, Ohden, Lisa, Davis-Keppen, Laura, Chitayat, David, Dowling, James J, Finkel, Richard, Dauber, Andrew, Spillmann, Rebecca, Pena, Loren D M, Metcalfe, Kay, Splitt, Miranda, Lachlan, Katherine, McKee, Shane A, Hurst, Jane, Fitzpatrick, David R, Morton, Jenny E V, Cox, Helen, Venkateswaran, Sunita, Young, Juan I, Marsh, Eric D, Nelson, Stanley F, Martinez, Julian A, Graham, John M, Kini, Usha, Mackay, Joel P, Pierson, Tyler Mark |
| المساهمون: | Repositório da Universidade de Lisboa |
| بيانات النشر: | Springer Nature, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | GATAD2B, NuRD complex, Apraxia of speech, Chromatin remodeling, Macrocephaly |
| الوصف: | Copyright © 2020, American College of Medical Genetics and Genomics |
| الوصف (مترجم): | Purpose: Determination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND). Methods: Fifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex. Results: Subjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners. Conclusions: A consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly. Research reported in this paper was supported by the National Institutes of Health (NIH) Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under award number U01HG007672. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. GAND50’s seq+ analysis was supported by NIH National Center for Advancing Translational Science (NCATS) UCLA Clinical and Translational Science Institute (CTSI) grant number UL1TR001881. J.P.M. received funding from the National Health and Medical Research Council (APP1012161, APP1063301, APP1126357, APP1058916). T.M.P. and this research was supported by the Cedars-Sinai institutional funding program and the Cedars-Sinai Diana and Steve Marienhoff Fashion Industries Guild Endowed Fellowship in Pediatric Neuromuscular and the Fashion Industries Guild Endowed Fellowship for the Undiagnosed Diseases Program. T.M.P. is especially grateful for the wonderful and continued support from the Cedars-Sinai Fashion Industries Guild. |
| نوع الوثيقة: | journal article |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Genet Med. 2020 May;22(5):878-888; 1098-3600; 1530-0366 |
| DOI: | 10.1038/s41436-019-0747-z |
| الإتاحة: | http://hdl.handle.net/10451/44904Test |
| حقوق: | restricted access |
| رقم الانضمام: | rcaap.com.ul.repositorio.ul.pt.10451.44904 |
| قاعدة البيانات: | RCAAP |
| DOI: | 10.1038/s41436-019-0747-z |
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