Journal article
Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders
H Guo, E Bettella, PC Marcogliese, R Zhao, JC Andrews, TJ Nowakowski, MA Gillentine, K Hoekzema, T Wang, H Wu, S Jangam, C Liu, H Ni, MH Willemsen, BW van Bon, T Rinne, SJC Stevens, T Kleefstra, HG Brunner, HG Yntema Show all
Nature Communications | NATURE PORTFOLIO | Published : 2019
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 statistica..
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Funding Acknowledgements
We thank Tonia Brown for assistance in editing this manuscript. We thank all of the families participating in this study. We are grateful to all of the families at the participating SSC sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, E. Wijsman). We appreciate obtaining access to phenotypic data on SFARI Base. Approved researchers can obtain the SSC population dataset described in this study (https://www.sfari.org/resource/resources/simons-simplex-collection/) by applying at https://base.sfari.org.We would like to thank Drs. Emanuela Leonardi, Roberta Polli, Chiara Rigon, Ornella Galesi, and Giuseppe Calabrese for useful discussions and technical assistance. This work was supported by the following grants: the National Natural Science Foundation of China (NSFC 31671114, 81871079) to H.G.; Simons Foundation Autism Research Initiative (SFARI 303241) to E.E.E.; National Institutes of Health (NIH R01MH101221) to E.E.E.; NIH (R01MH100047) to R.A.B.; NIH (R01NS069605) to H.C.M.; NSFC (81330027, 81525007) to K.X.; Key R&D Program of Hunan Province (2018DK2016) to Z.H.; SFARI (491371) to T.J.N.; and a grant from the South Carolina Department of Disabilities to C.E.S. E.E.E. and H.J.B. are investigators of the Howard Hughes Medical Institute. This work is also supported by NIH (U54NS093793) to H.J.B., S.Y. and M.J.W.; H.J.B. is supported by NIH (R01GM067858, R24OD022005); S.Y. and M.F.W. by a Simons Foundation Functional Screen Award (368479). M.A.G. was supported by the U.S. National Institutes of Health (T32HG000035). We would like to thank Hongling Pan, Danqing Bei and Kai Yuan's lab for technical assistance. Confocal microscopy at Baylor College of Medicine is supported in part by NIH grant U54HD083092 to the Intellectual and Developmental Disabilities Research Center (IDDRC) Neurovisualization Core. P.C.M. is funded by CIHR and the Stand by Eli Foundation. J.C.A. is supported by NIH F32 (NS110174-01). WES for proband MA.p1 was provided by the University of Washington Center for Mendelian Genomics (UWCMG) and funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute grant HG006493 to Drs. Debbie Nickerson, Michael Bamshad, and Suzanne Leal. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.