The GRID1/GLUD1 homozygous variant p.Arg161His linked to intellectual disability and spastic paraplegia impairs excitatory synaptic transmission in the hippocampus
Weixuan Xue, Suzy Markossian, Frédéric Flamant, Bertrand Lambolez, Régine Hepp, Ludovic Tricoire · FENS Forum 2024
The ionotropic glutamate delta receptor GluD1, encoded by the GRID1 gene, is widely expressed in the nervous system and is involved in the formation, function, and plasticity of synapses. GluD1 does not bind glutamate, but instead cerebellin and D-serine, which allows the formation of trans-synaptic bridges, and triggers transmembrane signaling. We recently reported a homozygous missense variants of GRID1, p.Arg161His, associated with combined intellectual disability, spastic paraplegia and glaucoma. In vitro studies revealed that this mutation hampers metabotropic glutamate receptor mGlu1/5 s
ePoster · Neuroscience