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

University of Washington Center for Mendelian Genomics

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number4679
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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mutations
Psychiatry
Genes
disorders
proteins
Neuroglia
genes
Mutation
Pediatrics
epilepsy
Neurons
disabilities
Drosophila
disrupting
Brain
Language Development
Autistic Disorder
neurons
Intellectual Disability
brain

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders. / University of Washington Center for Mendelian Genomics.

In: Nature Communications, Vol. 10, No. 1, 4679, 01.12.2019.

Research output: Contribution to journalArticle

University of Washington Center for Mendelian Genomics. / Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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