Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/122230

In Collections

This item can be found in the following collections:

Guo, H.; Bettella, E.; Marcogliese, P.C.; Zhao, R.J.; Andrews, J.C.; Nowakowski, T.J.; ... ; Univ Washington Ctr Mendelian Geno (2019)

Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders

Article / Letter to editor
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...Show morePostsynaptic 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.Show less
All authors
Guo, H.; Bettella, E.; Marcogliese, P.C.; Zhao, R.J.; Andrews, J.C.; Nowakowski, T.J.; Gillentine, M.A.; Hoekzema, K.; Wang, T.Y.; Wu, H.D.; Jangam, S.; Liu, C.Y.; Ni, H.L.; Willemsen, M.H.; Bon, B.W. van; Rinne, T.; Stevens, S.J.C.; Kleefstra, T.; Brunner, H.G.; Yntema, H.G.; Long, M.; Zhao, W.J.; Hu, Z.M.; Colson, C.; Richard, N.; Schwartz, C.E.; Romano, C.; Castiglia, L.; Bottitta, M.; Dhar, S.U.; Erwin, D.J.; Emrick, L.; Keren, B.; Afenjar, A.; Zhu, B.S.; Bai, B.; Stankiewicz, P.; Herman, K.; Mercimek-Andrews, S.; Juusola, J.; Wilfert, A.B.; Abou Jamra, R.; Buttner, B.; Mefford, H.C.; Muir, A.M.; Scheffer, I.E.; Regan, B.M.; Malone, S.; Gecz, J.; Cobben, J.; Weiss, M.M.; Waisfisz, Q.; Bijlsma, E.K.; Hoffer, M.J.V.; Ruivenkamp, C.A.L.; Sartori, S.; Xia, F.; Rosenfeld, J.A.; Bernier, R.A.; Wangler, M.F.; Yamamoto, S.; Xia, K.; Stegmann, A.P.A.; Bellen, H.J.; Murgia, A.; Eichler, E.E.; Nickerson, D.A.; Bamshad, M.J.; Univ Washington Ctr Mendelian Geno
Date
2019-10-15
Journal
Nature Communications
Volume
10
DOI
doi:10.1038/s41467-019-12435-8