دورية أكاديمية
Role of CAMK2D in neurodevelopment and associated conditions.
| العنوان: | Role of CAMK2D in neurodevelopment and associated conditions. |
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| المؤلفون: | Rigter PMF; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands; ENCORE Expertise Centre for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands., de Konink C; ENCORE Expertise Centre for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands; Department of Neuroscience, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands., Dunn MJ; Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA., Proietti Onori M; ENCORE Expertise Centre for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands; Department of Neuroscience, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands., Humberson JB; Pediatric Specialty Care, University of Virginia Health, Charlottesville, VA 22903, USA., Thomas M; Division of Genetics, Department of Pediatrics, University of Virginia Children's, Charlottesville, VA 22903, USA., Barnes C; Division of Genetics, Department of Pediatrics, University of Virginia Children's, Charlottesville, VA 22903, USA., Prada CE; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Division of Genetics, Genomics, and Metabolism, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Fundacion Cardiovascular de Colombia, Bucaramanga, Colombia., Weaver KN; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Ryan TD; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Caluseriu O; Department of Medical Genetics, University of Alberta, Edmonton, AB T6G 2H7, Canada; Stollery Children's Hospital, Department of Medical Genetics, University of Alberta, Edmonton, AB T6G 2B7, Canada., Conway J; Stollery Children's Hospital, Department of Pediatrics, Division of Pediatric Cardiology, University of Alberta, Edmonton, AB T6G 2B7, Canada., Calamaro E; Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., Fong CT; Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., Wuyts W; Department of Medical Genetics, University of Antwerp and University Hospital of Antwerp, 2650 Edegem, Belgium., Meuwissen M; Department of Medical Genetics, University of Antwerp and University Hospital of Antwerp, 2650 Edegem, Belgium., Hordijk E; Department of Neuroscience, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands., Jonkers CN; Department of Neuroscience, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands., Anderson L; Department of Neuroscience, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands., Yuseinova B; Department of Neuroscience, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands., Polonia S; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands., Beysen D; Department of Paediatric Neurology, University Hospital of Antwerp, 2650 Edegem, Belgium; Department of Translational Neurosciences, University of Antwerp, 2650 Edegem, Belgium., Stark Z; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; Australian Genomics, Melbourne, VIC 3052, Australia., Savva E; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia., Poulton C; Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, WA 6008, Australia., McKenzie F; Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, WA 6008, Australia; School of Paediatrics and Child Health, University of Western Australia, Perth, WA 6009, Australia., Bhoj E; Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Bupp CP; Corewell Health & Helen DeVos Children's Hospital, Grand Rapids, MI 49503, USA., Bézieau S; Nantes Université, CHU Nantes, Service de Génétique Médicale, 44000 Nantes, France; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France., Mercier S; Nantes Université, CHU Nantes, Service de Génétique Médicale, 44000 Nantes, France; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France., Blevins A; GeneDx, Gaithersburg, MD 20877, USA., Wentzensen IM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Xia F; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Rosenfeld JA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics Laboratories, Houston, TX 77021, USA., Hsieh TC; Institute for Genomic Statistics and Bioinformatics, University of Bonn, 53127 Bonn, Germany., Krawitz PM; Institute for Genomic Statistics and Bioinformatics, University of Bonn, 53127 Bonn, Germany., Elbracht M; Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany., Veenma DCM; ENCORE Expertise Centre for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands; Sophia Children's Hospital, Erasmus Medical Center, Rotterdam 3015 CN, the Netherlands., Schulman H; Department of Neurobiology, Stanford University, School of Medicine, Stanford, CA 94305, USA; Panorama Research Institute, Sunnyvale, CA 94089, USA., Stratton MM; Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA., Küry S; Corewell Health & Helen DeVos Children's Hospital, Grand Rapids, MI 49503, USA; Nantes Université, CHU Nantes, Service de Génétique Médicale, 44000 Nantes, France. Electronic address: sebastien.kury@chu-nantes.fr., van Woerden GM; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands; ENCORE Expertise Centre for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands; Department of Neuroscience, Erasmus Medical Center, Rotterdam 3015 GD, the Netherlands. Electronic address: g.vanwoerden@erasmusmc.nl. |
| المصدر: | American journal of human genetics [Am J Hum Genet] 2024 Feb 01; Vol. 111 (2), pp. 364-382. Date of Electronic Publication: 2024 Jan 24. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6605 (Electronic) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2008- : [Cambridge, MA] : Cell Press Original Publication: Baltimore, American Society of Human Genetics. |
| مواضيع طبية MeSH: | Calcium-Calmodulin-Dependent Protein Kinase Type 2*/genetics , Calcium-Calmodulin-Dependent Protein Kinase Type 2*/metabolism , Cardiomyopathy, Dilated* , Intellectual Disability* , Neurodevelopmental Disorders*/genetics, Animals ; Humans ; Mice ; Heart |
| مستخلص: | The calcium/calmodulin-dependent protein kinase type 2 (CAMK2) family consists of four different isozymes, encoded by four different genes-CAMK2A, CAMK2B, CAMK2G, and CAMK2D-of which the first three have been associated recently with neurodevelopmental disorders. CAMK2D is one of the major CAMK2 proteins expressed in the heart and has been associated with cardiac anomalies. Although this CAMK2 isoform is also known to be one of the major CAMK2 subtypes expressed during early brain development, it has never been linked with neurodevelopmental disorders until now. Here we show that CAMK2D plays an important role in neurodevelopment not only in mice but also in humans. We identified eight individuals harboring heterozygous variants in CAMK2D who display symptoms of intellectual disability, delayed speech, behavioral problems, and dilated cardiomyopathy. The majority of the variants tested lead to a gain of function (GoF), which appears to cause both neurological problems and dilated cardiomyopathy. In contrast, loss-of-function (LoF) variants appear to induce only neurological symptoms. Together, we describe a cohort of individuals with neurodevelopmental disorders and cardiac anomalies, harboring pathogenic variants in CAMK2D, confirming an important role for the CAMK2D isozyme in both heart and brain function. Competing Interests: Declaration of interests The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratories. A.B. and I.M.W. are employees of GeneDx, LLC; H.S. is a consultant for Vasa Therapeutics (Poland). (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.) |
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| فهرسة مساهمة: | Keywords: CAMK2D; calcium/calmodulin-dependent protein kinase 2 delta; cardiomyopathy; intellectual disability; neurodevelopment |
| المشرفين على المادة: | EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) EC 2.7.11.17 (CAMK2D protein, human) |
| تواريخ الأحداث: | Date Created: 20240125 Date Completed: 20240214 Latest Revision: 20240725 |
| رمز التحديث: | 20240726 |
| مُعرف محوري في PubMed: | PMC10870144 |
| DOI: | 10.1016/j.ajhg.2023.12.016 |
| PMID: | 38272033 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1537-6605 |
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| DOI: | 10.1016/j.ajhg.2023.12.016 |