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

ABSTRACT: The metabotropic glutamate receptor 7 (mGlu7) is a G protein-coupled receptor that has been recently linked to neurodevelopmental disorders. This association is supported by the identification of GRM7 variants in patients with autism spectrum disorder, attention deficit hyperactivity disorder, and severe developmental delay. One GRM7 mutation previously reported in 2 patients results in a single amino acid change, I154T, within the mGlu7 ligand-binding domain. Here, we report 2 new patients with this mutation who present with severe developmental delay and epilepsy. Functional studies of the mGlu7-I154T mutant reveal that this substitution resulted in significant loss of mGlu7 protein expression in HEK293A cells and in mice. We show that this occurred posttranscriptionally at the level of

SUBMITTER: Fisher NM 

PROVIDER: S-EPMC7934925 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature