| BackgroundsTemporal lobe epilepsy (TLE) is a chronic neurological disease, which is characterized by recurrent and unprovoked seizures originating in the brain temporal lobe. TLE is a complex central nervous disease whose occurrence and development is influenced by the environmental and genetic factors, and susceptibility gene plays a crucial role for the occurrence of TLE as well as its different clinical phenotypes. Various studies suggested that brain-derived neurotrophic factor (BDNF) gene polymorphisms contributed to the development of many neurological disorders, however, whether BDNF Val66Met polymorphism is associated with epilepsy remains controversial. In our study, we tried to investigate the effects of this functional polymorphism on the occurrence of TLE and its clinical phenotypes, as well as the activity of its specific receptor TrkB.MethodsTLE patients and healthy control subjects of Chinese Han origin were recruited in our study, and case-control studies were employed to invest the association between BDNF Val66Met polymorphism and TLE as well as its clinical phenotypes, TaqMan method was used for BDNF Val66Met polymorphism genotyping.Normal PCR and site-directed mutagenesis PCR were used to amplify BDNFVal and BDNFMet gene sequences, and constructions of exprssion vector containing the target gene were transfected into 293T cells, and Western Blot method was used to detect the expression of this polymorphism’s specific receptor TrkB.ResultsBDNF Val66Met polymorphism was genotyped in 499 TLE patients and 1181 healthy control subjects. Our results showed that the frequency of Met allele was found to be lower in TLE patients compared with the control subjects (43.9% vs 48.6%,P=0.012,OR=0.83,95%CI=0.71-0.96), and the frequency of Met66 allele carriers in the TLE with hippocampal sclerosis (HS) was significantly lower than those non-carriers (20.5% vs 29.1%, P=0.040). However, we failed to find the difference between different genotypes and the exprssion of its specific receptor TrkB.Conclusions Our findings suggested that BDNF Val66Met polymorphism might be correlated with epileptogenesis, and Met66 allele might play a protective role against the occurrence of TLE.BackgroundsBenign epilepsy with centrotemporal spikes (BECTs) is an idiopathic partial epilepsy syndrome, with an onset between 3 and 13 years old. BECTs is the most common childhood epilepsy syndrome and it has a high genetic syndrome. However, previous studies failed to find out the disease causing gene, and BECTs has been suspected as low penetrance autosomal dominant genetic disease. Recent studies have found that GRIN2A mutation can lead to epilepsy aphasia syndromes including BECTs. In our experience, we amplified and sequenced GRIN2A gene in thirty-five BECTs patients in Chinese Han origin to find out gene mutations.MethodsGenomic DNA was extracted from peripheral blood leukocytes in thirty-five patients, the 12 exons and their flanking sequences of GRIN2A gene were amplified with PCR. Amplified productions were sequenced using Sanger sequencing to explore gene mutation, and online software of bioinformatics was used to evaluate the effect of GRIN2A gene mutation.ResμLtsA novel heterozygosis missense mutation GRIN2A c.C989T (p.P330L) was found in one of thirty-five BECTs patients using sanger sequencing, and this locus was a newly discovered gene mutation.ConclusionsThe conservation of GRIN2A protein might be affected by c.C989T (p.P330L) mutation, which was predicted to be a novel pathogenic mutation. |
PDF Full Text Request