Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/21924
Title: Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.
Authors: Guo, Hui;Bettella, Elisa;Marcogliese, Paul C;Zhao, Rongjuan;Andrews, Jonathan C;Nowakowski, Tomasz J;Gillentine, Madelyn A;Hoekzema, Kendra;Wang, Tianyun;Wu, Huidan;Jangam, Sharayu;Liu, Cenying;Ni, Hailun;Willemsen, Marjolein H;van Bon, Bregje W;Rinne, Tuula;Stevens, Servi J C;Kleefstra, Tjitske;Brunner, Han G;Yntema, Helger G;Long, Min;Zhao, Wenjing;Hu, Zhengmao;Colson, Cindy;Richard, Nicolas;Schwartz, Charles E;Romano, Corrado;Castiglia, Lucia;Bottitta, Maria;Dhar, Shweta U;Erwin, Deanna J;Emrick, Lisa;Keren, Boris;Afenjar, Alexandra;Zhu, Baosheng;Bai, Bing;Stankiewicz, Pawel;Herman, Kristin;Mercimek-Andrews, Saadet;Juusola, Jane;Wilfert, Amy B;Abou Jamra, Rami;Büttner, Benjamin;Mefford, Heather C;Muir, Alison M;Scheffer, Ingrid E;Regan, Brigid M;Malone, Stephen;Gecz, Jozef;Cobben, Jan;Weiss, Marjan M;Waisfisz, Quinten;Bijlsma, Emilia K;Hoffer, Mariëtte J V;Ruivenkamp, Claudia A L;Sartori, Stefano;Xia, Fan;Rosenfeld, Jill A;Bernier, Raphael A;Wangler, Michael F;Yamamoto, Shinya;Xia, Kun;Stegmann, Alexander P A;Bellen, Hugo J;Murgia, Alessandra;Eichler, Evan E
Affiliation: Greenwood Genetic Center, Greenwood, SC, 29646, USA
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA
Departments of Medicine and Paediatrics, The University of Melbourne, Royal Children's Hospital, Melbourne, VIC, 3084, Australia
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, 77030, USA
Program in Developmental Biology, Baylor College of Medicine, Houston, TX, 77030, USA
Department of Neuroscience, Baylor College of Medicine, Houston, TX, 77030, USA
Department of Human Genetics, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands
Department of Clinical Genetics, Maastricht University Medical Center, 6202 AZ, Maastricht, The Netherlands..
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 410078, Changsha, Hunan, China
Hunan Key Laboratory of Animal Models for Human Diseases, 410078, Changsha, Hunan, China..
Emma Children's Hospital AUMC, 1105 AZ, Amsterdam, The Netherlands
North West Thames Genetics Service NHS, London, UK..
Department of Pediatrics, The First People's Hospital of Yunnan Province, 650032, Kunming, Yunnan, China
Medical Faculty, Kunming University of Science and Technology, 650032, Kunming, Yunnan, China
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 410078, Changsha, Hunan, China
UCSF Department of Anatomy, University of California, San Francisco, San Francisco, CA, 94143, USA
UCSF Department of Psychiatry, University of California, San Francisco, San Francisco, CA, 94143, USA
Laboratory of Molecular Genetics of Neurodevelopment, Department of Women's and Children's Health, University of Padua, Via Giustiniani 3, 35128, Padua, Italy
Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35129, Padua, Italy
School of Medicine and the Robinson Research Institute, The University of Adelaide at the Women's and Children's Hospital, Adelaide, SA, 5006, Australia
Department of Neurosciences, Queensland Children's Hospital, Brisbane, QLD, 4101, Australia
UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 94158, USA
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA
Howard Hughes Medical Institute, University of Washington, Seattle, WA, 98195, USA
Department of Psychiatry, University of Washington, Seattle, WA, 98195, USA
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA, 98195, USA
GeneDx, Gaithersburg, MD, 20877, USA
Section of Medical Genomics, Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento, CA, 95817, USA
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 410078, Changsha, Hunan, China
Department of Human Genetics, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands
Department of Clinical Genetics, Maastricht University Medical Center, 6202 AZ, Maastricht, The Netherlands
Department of Human Genetics, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 410078, Changsha, Hunan, China
Normandie Univ, UNICAEN, CHU de Caen Normandie, Department of Genetics, EA7450 BioTARGen, 14000, Caen, France
Oasi Research Institute-IRCCS, 94108, Troina, Italy
Département de génétique, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, 75013, Paris, France
APHP, Centre de référence des malformations et maladies congénitales du cervelet Département de génétique et embryologie médicale, GRCn°19, pathologies Congénitales du Cervelet-LeucoDystrophies, AP-HP, Hôpital Armand Trousseau, F-75012, Paris, France
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada
Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Clinical Genetics, Amsterdam, Netherlands
Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands
Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, 35128, Padua, Italy
Laboratory of Molecular Genetics of Neurodevelopment, Department of Women's and Children's Health, University of Padua, Via Giustiniani 3, 35128, Padua, Italy
Issue Date: 15-Oct-2019
EDate: 2019-10-15
Citation: Nature communications 2019; 10(1): 4679
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21924
DOI: 10.1038/s41467-019-12435-8
ORCID: 0000-0002-1570-2545
0000-0002-8011-7852
0000-0003-2345-4964
0000-0003-0702-7399
0000-0002-7770-1943
0000-0003-1049-0683
0000-0001-8396-6764
0000-0001-8590-222X
0000-0002-1542-1399
0000-0002-9420-085X
0000-0002-7884-6861
0000-0002-0936-1406
0000-0002-0012-6848
0000-0002-4974-9851
0000-0003-2172-8036
0000-0001-5992-5989
0000-0001-6788-0653
0000-0002-8246-4014
0000-0002-2311-2174
PubMed URL: 31616000
Type: Journal Article
Appears in Collections:Journal articles

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