机构：[1]Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.[2]Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 410078 Changsha, Hunan, China.[3]Laboratory of Molecular Genetics of Neurodevelopment, Department of Women’s and Children’s Health, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.[4]Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35129 Padua, Italy.[5]Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.[6]Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA.[7]UCSF Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.[8]UCSF Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA.[9]UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.[10]Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.[11]Department of Clinical Genetics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands.[12]Normandie Univ, UNICAEN, CHU de Caen Normandie, Department of Genetics, EA7450 BioTARGen, 14000 Caen, France.[13]Greenwood Genetic Center, Greenwood, SC 29646, USA.[14]Oasi Research Institute-IRCCS, 94108 Troina, Italy.[15]Département de génétique, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, 75013 Paris, France.[16]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.[17]Department of Pediatrics, The First People’s Hospital of Yunnan Province, 650032 Kunming, Yunnan, China.内科片儿科云南省第一人民医院[18]Medical Faculty, Kunming University of Science and Technology, 650032 Kunming, Yunnan, China.[19]Section of Medical Genomics, Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento, CA 95817, USA.[20]Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA 98195, USA.[21]Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.[22]GeneDx, Gaithersburg, MD 20877, USA.[23]Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.[24]Departments of Medicine and Paediatrics, The University of Melbourne, Austin Health and Royal Children’s Hospital, Melbourne, VIC 3084, Australia.[25]Department of Neurosciences, Queensland Children’s Hospital, Brisbane, QLD 4101, Australia.[26]School of Medicine and the Robinson Research Institute, The University of Adelaide at the Women’s and Children’s Hospital, Adelaide, SA 5006, Australia.[27]Emma Children’s Hospital AUMC, 1105 AZ Amsterdam, The Netherlands.[28]North West Thames Genetics Service NHS, London, UK.[29]Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Clinical Genetics, Amsterdam, Netherlands.[30]Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.[31]Paediatric Neurology and Neurophysiology Unit, Department of Women’s and Children’s Health, University Hospital of Padua, 35128 Padua, Italy.[32]Department of Psychiatry, University of Washington, Seattle, WA 98195, USA.[33]Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.[34]Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.[35]Hunan Key Laboratory of Animal Models for Human Diseases, 410078 Changsha, Hunan, China.[36]Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.[37]Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [NSFC 31671114, 81871079]; Simons Foundation Autism Research Initiative [SFARI 303241]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIH R01MH101221]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01MH100047, R01NS069605, U54NS093793, R01GM067858, R24OD022005, U54HD083092]; NSFCNational Natural Science Foundation of China [81330027, 81525007]; Key R&D Program of Hunan Province [2018DK2016]; SFARI [491371]; South Carolina Department of Disabilities; Simons Foundation Functional Screen Award [368479]; U.S. National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32HG000035]; CIHRCanadian Institutes of Health Research (CIHR); Stand by Eli Foundation; NIH F32United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NS110174-01]; National Human Genome Research InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI); National Heart, Lung and Blood Institute grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [HG006493]
第一作者机构：[1]Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.[2]Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 410078 Changsha, Hunan, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.[37]Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
推荐引用方式(GB/T 7714)：
Guo Hui,Bettella Elisa,Marcogliese Paul C.,et al.Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders[J].NATURE COMMUNICATIONS.2019,10:doi:10.1038/s41467-019-12435-8.
APA：
Guo, Hui,Bettella, Elisa,Marcogliese, Paul C.,Zhao, Rongjuan,Andrews, Jonathan C....&Evan E. Eichler.(2019).Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.NATURE COMMUNICATIONS,10,
MLA：
Guo, Hui,et al."Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders".NATURE COMMUNICATIONS 10.(2019)
综合性期刊