A GRM7 mutation associated with developmental delay reduces mGlu7 expression and produces neurological phenotypes

• DOI: 10.1172/jci.insight.143324
• Publication Date: 2021-01-21T17:01:40Z
• Authors: Nicole M. Fisher; Aqeela AlHashim; Aditi B. Buch; Hana Badivuku; Manar M. Samman; Kelly M. Weiss; Gabriela I. Cestero; Mark D. Does; Jerri M. Rook; Craig W. Lindsley; P. Jeffrey Conn; Rocco G. Gogliotti; Colleen M. Niswender
• Keywords: Neurodevelopmental disorder

The metabotropic glutamate receptor 7 (mGlu7) is a G protein–coupled that has been recently linked to neurodevelopmental disorders. This association supported by the identification of GRM7 variants in patients with autism spectrum disorder, attention deficit hyperactivity and severe developmental delay. One mutation previously reported 2 results single amino acid change, I154T, within mGlu7 ligand-binding domain. Here, we report new this who present delay epilepsy. Functional studies mGlu7-I154T mutant reveal substitution resulted significant loss protein expression HEK293A cells mice. We show occurred posttranscriptionally at level trafficking. Similar mGlu7–global KO mice, animals exhibited reduced motor coordination, deficits contextual fear learning, seizures. provides functional evidence disease-associated affecting was sufficient cause neurological dysfunction mice further validates as disease-causing gene human population.