Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders
Year: 2019
Type: article
Study design: Observational Study
Abstract: Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
Source: Nature Communications
Authors: Hui Guo, Elisa Bettella, Paul C. Marcogliese, Rongjuan Zhao, Jonathan C. Andrews, Tomasz J. Nowakowski, Madelyn A. Gillentine, Kendra Hoekzema, Tianyun Wang, Huidan Wu, Sharayu Jangam, Cenying Liu, Hailun Ni, Marjolein H. Willemsen, Bregje W. van Bon, Tuula Rinne, Servi J. C. Stevens, Tjitske Kleefstra, Han G. Brunner, Helger G. Yntema, Min Long, Wenjing Zhao, Zhengmao Hu, Cindy Colson, Nicolas Richard, Charles E. Schwartz, Corrado Romano, Lucia Castiglia, Maria Bottitta, Shweta U. Dhar, Deanna J. Erwin, Lisa Emrick, Boris Keren, Alexandra Afenjar, Baosheng Zhu, Bing Bai, Pawel Stankiewicz, Kristin Herman, Deborah A. Nickerson, Michael J. Bamshad, Saadet Mercimek-Andrews, Jane Juusola, Amy B. Wilfert, Rami Abou Jamra, Benjamin Büttner, Heather C. Mefford, Alison M. Muir, Ingrid E. Scheffer, Brigid M. Regan, Stephen Malone, Jozef Gecz, Jan Cobben, Marjan M. Weiss, Quinten Waisfisz, Emilia K. Bijlsma, Mariëtte J. V. Hoffer, Claudia A. L. Ruivenkamp, Stefano Sartori, Fan Xia, Jill A. Rosenfeld, Raphael A. Bernier, Michael F. Wangler, Shinya Yamamoto, Kun Xia, Alexander P. A. Stegmann, Hugo J. Bellen, Alessandra Murgia, Evan E. Eichler
Institutions: Central South University, University of Washington, Chinese Academy of Forestry, University of Padua, Azienda Ospedale - Università Padova, Città della Speranza Foundation, Baylor College of Medicine, Texas Children's Hospital, University of California, San Francisco, Washington University in St. Louis, Radboud University Nijmegen, Maastricht University Medical Centre, Radboud University Medical Center, Maastricht University, Centre Hospitalier Universitaire de Caen Normandie, Biologie, Génétique et Thérapies ostéoArticulaires et Respiratoires, Université de Caen Normandie, Greenwood Genetic Center, Istituti di Ricovero e Cura a Carattere Scientifico, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Institut du Cerveau, Hôpital Armand-Trousseau, Kunming University of Science and Technology, First People's Hospital of Yunnan Province, University of California, Davis, University of Toronto, Hospital for Sick Children, Leipzig University, University Hospital Leipzig, The University of Melbourne, Royal Children's Hospital, QIMR Berghofer Medical Research Institute, Austin Health, The University of Adelaide, Emma Kinderziekenhuis, Children's Health Queensland Hospital and Health Service, Women's and Children's Hospital, Vrije Universiteit Amsterdam, Leiden University Medical Center, Amsterdam University Medical Centers, Chinese University of Hong Kong, Howard Hughes Medical Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Howard Hughes Medical Institute, U.S. Department of Health and Human Services, Simons Foundation, University of Washington, Simons Foundation Autism Research Initiative, National Natural Science Foundation of China, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, Center for Mendelian Genomics, University of Washington, Canadian Institutes of Health Research, National Institute of Mental Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1043988108, G1068064772, G1139066663, Rare Mutations and Autism Spectrum Disorders, G1523804307, G1869294642, G3021313697, G3180509009, G3453817081, G3622009640, G4102661714, G4177649312, G4444814008, CSDE1基因组转录后调控及其在神经发育和孤独症发生中的作用机制研究, G4754858258, G49683581, G5932874884, G6250650901, Center for functional analysis of human UDN gene homologs in Drosophila and zebrafish, G6399379275, G654541330, G664261826, G6864174283, G6905538592, G7189368291, G7724140786, 儿童孤独症的神经环路机制研究, G8216675651, UW Center for Mendelian Genomics, A Comprehensive Resource for Manipulating the Drosophila Genome, G9000005034, G9000023684, G9000056630, G9000074939, G9000109313, G9000175825, G9000181635, G9000274663, G9000345790, Interdisciplinary Training in Genome Sciences, A Human cDNA Library for Functional Gene Replacement in Drosophila
OpenAlex ID: W2980441224