Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects

Authors: Dennis Mircsof , Maéva Langouët , Marlène Rio, Sébastien Moutton , Karine Siquier-Pernet , Christine Bole-Feysot , Nicolas Cagnard , Patrick Nitschke , Ludmila Gaspar , Matej Žnidarič , Olivier Alibeu , Ann-Kristina Fritz , David P Wolfer , Aileen Schröter , Giovanna Bosshard , Markus Rudin , Christina Koester , Florence Crestani , Petra Seebeck , Nathalie Boddaert , Katrina Prescott , DDD Study; Rochelle Hines, Steven J Moss , Jean-Marc Fritschy , Arnold Munnich , Jeanne Amiel , Steven A Brown , Shiva K Tyagarajan , Laurence Colleaux

DOI: 10.1038/nn.4169

Abstract

The NONO protein has been characterized as an important transcriptional regulator in diverse cellular contexts. Here we show that loss of NONO function is a likely cause of human intellectual disability and that NONO-deficient mice have cognitive and affective deficits. Correspondingly, we find specific defects at inhibitory synapses, where NONO regulates synaptic transcription and gephyrin scaffold structure. Our data identify NONO as a possible neurodevelopmental disease gene and highlight the key role of the DBHS protein family in functional organization of GABAergic synapses.

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