Closed
Targeted gene(s)/phenotype:
GRIA1 (#138248), GRIA2 (#618917), GRIA3 (#300699), and GRIA4 (#617864)
Abstract
GRIA genes encode AMPAR receptors which are important for the function of excitatory neurons. Disease-causing variants in GRIA, GRIA2, GRIA3, and GRIA4 cause a neurodevelopmental disorder (NDD) with mild-profound developmental and cognitive impairment, behavioral difficulties, early-onset and treatment-resistant seizures. Only few patients have been reported leaving phenotypical spectrum and genotype-phenotype correlations ill-defined.
We want to:
- collect clinical data from patients with rare GRIAvariants in order to establish a database of high-quality genetic and clinical data sets.
- Systematically evaluate the impact of GRIAvariants on key parameters of AMPAR function using a combination of biochemical and functional assays and advanced electrophysiology to pinpoint exact phenotypical mutational impact on AMPAR molecular function and classify pathogenicity of variants.
- Analyze correlations between patient disease phenotypes and specific effects on receptor function to establish genotype-phenotype patterns and perform pilot experiments to explore options for rescue pharmacology using existing AMPAR drugs.
Coordinating clinicians/researchers
Allan Bayat
Contact email: abaya@filadelfia.dk, bayabayabayat@hotmail.com
Institution
Department of Epilepsy Genetics and Personalized Medicine
Danish Epilepsy Centre Filadelfia
Dianalund, Denmark
Specific requirements beyond clinical data and genotype data sharing
- Re-analysis of DNA samples: No
- Resampling of patients: No
- Linked to a translational/basic research project: Yes