Most of the hereditary idiopathic epilepsies are due to mutation in ionchannels expressed in brain. Recently two non-ion channel genes LGI1 andVGLR1 have emerged as important causes of specific epilepsy syndromes. Theproduct of these two genes share a conserved repeated region of about 44 aminoacid residues, the EAR domain (for epilepsy-associated repeat) [].The predicted secondary structure (four β-strands) and the numbers ofrepeated copies (seven) suggest that the EAR domain belongs to theβ-propeller fold. A common functional feature found in all characteriseddomains of this class is a participation in protein-protein interactions.Since the EAR repeat is found in the ectodomain of VLGR1, it is most probablyinvolved in ligand recognition by the receptor [].Proteins known to contain EAR repeats are listed below:Mammalian LGI1 to LGI4. LGI1 is mutated in autosomal dominant partialepilepsy with auditory features (ADPEAF). The F348C missense mutation islocated in the third EAR repeat (7 copies).Mammalian thrombo-spondin N-terminal domain and EAR repeats containgprotein (TSPEAR) (7 copies).Mammalian very large G protein-coupled receptor 1 (VGLR1) or monogenicaudiogenic seizure-susceptible (MASS1) protein. In mouse, mutations inMASS1 gene are associated with generalized epilepsy and seizures inresponse to loud noises (7 copies) [].
