De novo mutations in the GABBR2 gene are associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM 617904) (EuroEPINOMICS-RES Consortium 2014; Hamdan et al., 2017), as well as with a Rett syndrome-like disorder called neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM 617903) (Lopes et al., 2016; Yoo et al., 2017; Vuillaume et al., 2018). One individual with GABBR2-mediated epileptic encephalopathy that was reported in EuroEPINOMICS-RES Consortium 2014 also presented with autism spectrum disorder, whereas individuals with GABBR2-mediated NDPLHS have been reported with autism spectrum disorder, autistic features, and/or stereotypic hand movements. The same recurrent de novo missense variant in GABBR2 that was observed in individuals from Lopes et al., 2016 and Yoo et al., 2017 (p.Ala567Thr) was also identified in a Japanese ASD proband in Takata et al., 2018.
Molecular Function
The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies.
Early infantile epileptic encephalopathy-59 (EIEE5
