Media type: E-Article Title: Neuroligin 2 nonsense variant associated with anxiety, autism, intellectual disability, hyperphagia, and obesity Contributor: Parente, Daniel J.; Garriga, Caryn; Baskin, Berivan; Douglas, Ganka; Cho, Megan T.; Araujo, Gabriel C.; Shinawi, Marwan Published: Wiley, 2017 Published in: American Journal of Medical Genetics Part A, 173 (2017) 1, Seite 213-216 Language: English DOI: 10.1002/ajmg.a.37977 ISSN: 1552-4825; 1552-4833 Origination: Footnote: Description: <jats:sec><jats:label /><jats:p>Neuroligins are post‐synaptic, cellular adhesion molecules implicated in synaptic formation and function. NLGN2 is strongly linked to inhibitory, GABAergic signaling and is crucial for maintaining the excitation‐inhibition balance in the brain. Disruption of the excitation‐inhibition balance is associated with neuropsychiatric disease. In animal models, altered <jats:italic>NLGN2</jats:italic> expression causes anxiety, developmental delay, motor discoordination, social impairment, aggression, and sensory processing defects. In humans, mutations in <jats:italic>NLGN3</jats:italic> and <jats:italic>NLGN4</jats:italic> are linked to autism and schizophrenia; <jats:italic>NLGN2</jats:italic> missense variants are implicated in schizophrenia. Copy number variants encompassing <jats:italic>NLGN2</jats:italic> on 17p13.1 are associated with autism, intellectual disability, metabolic syndrome, diabetes, and dysmorphic features, but an isolated <jats:italic>NLGN2</jats:italic> nonsense variant has not yet been described in humans. Here, we describe a 15‐year‐old male with severe anxiety, obsessive‐compulsive behaviors, developmental delay, autism, obesity, macrocephaly, and some dysmorphic features. Exome sequencing identified a heterozygous, de novo, c.441C>A p.(Tyr147Ter) variant in <jats:italic>NLGN2</jats:italic> that is predicted to cause loss of normal protein function. This is the first report of an <jats:italic>NLGN2</jats:italic> nonsense variant in humans, adding to the accumulating evidence that links synaptic proteins with a spectrum of neurodevelopmental phenotypes. © 2016 Wiley Periodicals, Inc.</jats:p></jats:sec>