[Molecular genetics of epilepsy].
Recent identifications of genes responsible for epilepsies are now contributing to diagnosis and treatment. Mutations of voltage-gated sodium channel genes SCN1A and SCN2A have been reported in epilepsies with a variety of phenotypes including generalized epilepsy with febrile seizures plus (GEFS +), severe myoclonic epilepsy in infancy (SMEI), intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), and benign familial neonatal-infantile seizures (BFNIS). We also identified a sporadic nonsense mutation of SCN2A in a patient with intractable epilepsy with severe mental decline. Lafora's disease (LD) is a fatal autosomal recessive epilepsy characterized by stimuli sensitive myoclonus, grand mal seizures, and progressive intellectual and neurological deterioration. The EPM2A gene has been reported to be responsible for LD. We found multiple disease mutations of EPM2A in LD patients, and also identified a subclass of LD who shows an early onset cognitive defect and correlated with EPM2A exon 1 mutations. We reported that the laforin protein encoded by the EPM2A gene has a dual-specificity phosphatase activity, associates with polyribosome, and interacts with the HIRIP5 protein with NifU-like domain. We recently generated and reported the EPM2A KO mice those develop neurodegeneration and other features similar to those of LD patients.
Yamakawa
Kazuhiro
K
Riken Brain Science Institute.
D002648:Child; D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D007223:Infant; D020192:Lafora Disease / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D062548:Voltage-Gated Sodium Channel beta-2 Subunit
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; C117620:SCN2B protein, human; C568249:Scn1a protein, mouse; D015222:Sodium Channels; D062548:Voltage-Gated Sodium Channel beta-2 Subunit