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

2019-10-15

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

Journal Article

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

10.1038/s41467-019-12435-8

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.

link

Nature Communications 2019; 10(1): 4679

Nature Communications