Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer.
In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Help us improve our products. Sign up to take part. A Nature Research Journal. 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 βwhose 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.
NDDs show a wide range of overlapping clinical features, which pose serious challenges for diagnoses based exclusively on clinical criteria. Despite the exponential increase in the number of associated genes, the genetic basis for more than half of cases remains unknown, in large part, due to the rarity of particular genetic subtypes and more complex genetic patterns of inheritance e.
