학술논문
Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.
Document Type
article
Author
Guo, Hui; Bettella, Elisa; Marcogliese, Paul; Zhao, Rongjuan; Andrews, Jonathan; Nowakowski, Tomasz; Gillentine, Madelyn; Hoekzema, Kendra; Wang, Tianyun; Wu, Huidan; Jangam, Sharayu; Liu, Cenying; Ni, Hailun; Willemsen, Marjolein; van Bon, Bregje; Rinne, Tuula; Stevens, Servi; Kleefstra, Tjitske; Brunner, Han; Yntema, Helger; Long, Min; Zhao, Wenjing; Hu, Zhengmao; Colson, Cindy; Richard, Nicolas; Schwartz, Charles; Romano, Corrado; Castiglia, Lucia; Bottitta, Maria; Dhar, Shweta; Erwin, Deanna; Emrick, Lisa; Keren, Boris; Afenjar, Alexandra; Zhu, Baosheng; Bai, Bing; Stankiewicz, Pawel; Mercimek-Andrews, Saadet; Juusola, Jane; Wilfert, Amy; Abou Jamra, Rami; Büttner, Benjamin; Mefford, Heather; Muir, Alison; Scheffer, Ingrid; Regan, Brigid; Malone, Stephen; Gecz, Jozef; Cobben, Jan; Weiss, Marjan; Waisfisz, Quinten; Bijlsma, Emilia; Hoffer, Mariëtte; Ruivenkamp, Claudia; Sartori, Stefano; Xia, Fan; Rosenfeld, Jill; Bernier, Raphael; Wangler, Michael; Yamamoto, Shinya; Xia, Kun; Stegmann, Alexander; Bellen, Hugo; Murgia, Alessandra; Eichler, Evan; Herman, Kristin
Source
Nature Communications. 10(1)
Subject
Language
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.