Mutations Of GABRG2 Gene In The Patients Affected With Mesial Temporal Lobe Epilepsy

Epilepsy (EP) is an intermittent disorder of the nervous system due presumably to a sudden, excessive, disorderly discharge of cerebral neurons. This discharge results in an almost instantaneous disturbance of sensation, loss of consciousness, convulsive movements, or some combination thereof. Moutains of evidences from laboratary and clinical data show that gene abnormality is the major etiological factor of over 40% patients affected with epilepsy.There were also 6 epilepsy genes been cloned successfully, and mutations of over 1000 genes maybe related to epilepsy. These abnormal genes influence many aspects from molecular level to the neuronal plasticity, such as the development of brain,neuronic degeneration, remodeling of neural circuits, energy metabolism, ion channel and so on.These factors would at last affect the formation of epilepsy focus, propagations of epileptic potentials, vulnerability of epilepsy cells. Almost all these mutations were found in genes encoding ion channel proteins. In recent years,mutations of gene encoding gamma-aminobutyric acid A-receptor γ2 subunit (GABRG2) were founded linked to many kinds of epilepsy syndromes such as Febrile Seizure(FS), Generalized Epilepsy with Febrile Seizure plus(GEFS+), Childhood Absence Epilepy(CAE), Severe Myoclonic Epilepsy of Infancy(SMEI).Some of them would develop to another epilepsy syndrome. A significant proportion of patients affected with medial temporal lobe epilepsy (MTLE) had antecedents of prolonged febrile seizures in the early childhood. Prolonged febrile seizure would bring damage to the hippocampus and was therefore a cause of hippocampal sclerosis.Meanwhile, the most significant pathological change of MTLE was hippocampal sclerosis.In our study, we supposed that there were mutations of GABRG2 gene in patients with MTLE.So we amplified cDNA of GABRG2 gene from some patients with MTLE,and then sequenced the cDNA.We found a C.245G→A nucleotide substitution in exon 2(a R43Q mutation in muture GABRG2 protein). Then we sceened the mutant patients and somehealthy people. The main results are as follows:1. cDNA of GABRG2 gene was sucssesfully amplified from some patients with MTLE, and then sequenced.2. The C.245G—A nucleotide substitution in exon 2 of GABRG2 gene has been identified in this experiment.In conclusion, we successfully amplified cDNA of GABRG2 gene from some patients with MTLE, and then sequenced it. And we identified a significent mutation, C.245G—A, in exon 2 of GABRG2 gene. This mutation would be a major reason for the tolerance in some patients with MTLE.