DLG4-related synaptopathy: a new rare brain disorder
Autor: | Edgard Verdura, Alex MacKenzie, Rolph Pfundt, Tobias B. Haack, Ange Line Bruel, Paulino Gómez-Puertas, Anna C.E. Hurst, Bert B.A. de Vries, Stella A. de Man, Maria Johansson Soller, Bregje W.M. van Bon, Elisabeth Sarrazin, Agustí Rodríguez-Palmero, Stephan Waldmüller, Melanie O’Leary, Anne Sophie Denommé-Pichon, Bitten Schönewolf-Greulich, Joseph T. Shieh, V. A. Bjerregaard, Vahid Bahrambeigi, Malin Kvarnung, Agatha Schlüter, Anne Marie Bisgaard, Ingrid M.B.H. van de Laar, Elisa Giorgio, Lars Feuk, Mieke M. van Haelst, Thomas D. Challman, Ineke van de Burgt, Sulagna Kushary, Simone F. Reiter, David B. Everman, Zeynep Tümer, Giorgia Mandrile, Conny M. A. van Ravenswaaij-Arts, Charles Shaw-Smith, Juliane Hoyer, Chad R. Haldeman-Englert, Lotte Kleinendorst, Bryce A. Mendelsohn, Anna Lindstrand, Christine Coubes, Gea Beunders, Sixto García-Miñaur, Antonio Vitobello, Melissa Maria Boerrigter, Alysia Kern Lovgren, Anya Revah-Politi, Carlos E. Prada, Bertrand Isidor, Elena Repnikova, Stephanie Spranger, Esmée van Drie, Frédéric Tran Mau-Them, Zohra Shad, Ben Pode-Shakked, Aurora Pujol, Christiane Zweier, Bjørn Ivar Haukanes, David Gómez-Andrés, Kathleen A. Leppig, Marta Pacio-Míguez, Motti Shohat, Yuval Landau, Benjamin Cogné, Frances Elmslie, Kimberly A. Aldinger, Anita Rauch, Juliann M. Savatt, Nicolas Gruchy, Sharon Whiting, William B. Dobyns, Thomas J. Dye, Sebastien Moutton, Heidi Thiese, Setareh Moghadasi, Iñigo Marcos-Alcalde, Jenny Morton, Sumit Parikh, María Palomares-Bralo, Stéphanie Arpin, Tracy S. Gertler, Meredith J. Ross, Bernt Popp, Amelie J. Müller, Claudia A. L. Ruivenkamp |
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Přispěvatelé: | Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), CIBER de Enfermedades Raras (CIBERER), Hospital Universitario Germans Trias I Pujol, Vall d'Hebron University Hospital [Barcelona], Center for Integrative Brain Research [Seattle, WA, USA], University of Washington [Seattle]-Seattle Children's Research Institute, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Department of Molecular and Human Genetics (Baylor College of Medicine), Baylor College of Medecine, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Clinical Genetics, Human Genetics, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D) |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Autism Spectrum Disorder [SDV]Life Sciences [q-bio] 030105 genetics & heredity Biology 03 medical and health sciences Intellectual Disability Intellectual disability medicine Missense mutation Humans Global developmental delay Exome Genetics (clinical) Genetics Brain Diseases Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] Brain medicine.disease 030104 developmental biology Phenotype Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] Autism spectrum disorder Neurodevelopmental Disorders Synaptopathy DLG4 Postsynaptic density Disks Large Homolog 4 Protein |
Zdroj: | Genetics in Medicine Genetics in Medicine, Nature Publishing Group, 2021, ⟨10.1038/s41436-020-01075-9⟩ Rodríguez-Palmero, A, Boerrigter, M M, Gómez-Andrés, D, Aldinger, K A, Marcos-Alcalde, Í, Popp, B, Everman, D B, Lovgren, A K, Arpin, S, Bahrambeigi, V, Beunders, G, Bisgaard, A M, Bjerregaard, V A, Bruel, A L, Challman, T D, Cogné, B, Coubes, C, de Man, S A, Denommé-Pichon, A S, Dye, T J, Elmslie, F, Feuk, L, García-Miñaúr, S, Gertler, T, Giorgio, E, Gruchy, N, Haack, T B, Haldeman-Englert, C R, Haukanes, B I, Hoyer, J, Hurst, A C E, Isidor, B, Soller, M J, Kushary, S, Kvarnung, M, Landau, Y E, Leppig, K A, Lindstrand, A, Kleinendorst, L, MacKenzie, A, Mandrile, G, Mendelsohn, B A, Moghadasi, S, Morton, J E, Moutton, S, Müller, A J, O’Leary, M, Pacio-Míguez, M, Palomares-Bralo, M, Parikh, S, Pfundt, R, Pode-Shakked, B, Rauch, A, Repnikova, E, Revah-Politi, A, Ross, M J, Ruivenkamp, C A L, Sarrazin, E, Savatt, J M, Schlüter, A, Schönewolf-Greulich, B, Shad, Z, Shaw-Smith, C, Shieh, J T, Shohat, M, Spranger, S, Thiese, H, Mau-Them, F T, van Bon, B, van de Burgt, I, van de Laar, I M B H, van Drie, E, van Haelst, M M, van Ravenswaaij-Arts, C M, Verdura, E, Vitobello, A, Waldmüller, S, Whiting, S, Zweier, C, Prada, C E, de Vries, B B A, Dobyns, W B, Reiter, S F, Gómez-Puertas, P, Pujol, A & Tümer, Z 2021, ' DLG4-related synaptopathy : a new rare brain disorder ', Genetics in Medicine, vol. 23, no. 5, pp. 888-899 . https://doi.org/10.1038/s41436-020-01075-9 Genetics in Medicine, 23(5), 888-899. Lippincott Williams & Wilkins Genetics in medicine, 23(5), 888-899. Lippincott Williams and Wilkins Genetics in Medicine, 23, 5, pp. 888-899 r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname Genetics in Medicine. Nature Publishing Group Genetics in Medicine, 23(5), 888-899. SPRINGERNATURE Genetics in Medicine, 23, 888-899 DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria Genetics in Medicine, 23(5), 888-899. Lippincott Williams and Wilkins |
ISSN: | 1098-3600 |
Popis: | Contains fulltext : 245031.pdf (Publisher’s version ) (Closed access) PURPOSE: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants. METHODS: The clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing. RESULTS: The clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit-hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies. CONCLUSION: The present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy. |
Databáze: | OpenAIRE |
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