Investigation of the possible association of NEDD4-2 (NEDD4L) gene with idiopathic photosensitive epilepsy.

NEDD4-2 alias NEDD4L (neural precursor cell expressed, developmentally downregulated) gene was reported as a candidate gene for epileptic photo-sensitivity. We aimed to investigate this possible association of NEDD4-2 variants with idiopathic photosensitive epilepsy. Consecutive patients who had been followed up at our epilepsy center and diagnosed with idiopathic epilepsy according to ILAE criteria and clear-cut photoparoxysmal responses in their electroencephalograms and 100 ethnically matched healthy subjects were included in the study. The regions around previously reported three variants, namely, S233L, E271A and H515P were tracked with DHPLC and the samples showing variations were sequenced. 81 patients (63 females) aged between 12-63 years (45 had juvenile myoclonic epilepsy, 11 childhood absence epilepsy, 14 juvenile absence epilepsy, 7 late onset idiopathic generalized epilepsy, 1 unclassified idiopathic generalized epilepsy, and 3 patients with idiopathic photosensitive occipital lobe epilepsy) were included in this study. We found only one heterozygous S233L variant in a 23-year-old man who has photosensitive form of juvenile absence epilepsy and pattern sensitivity to striped carpets. Other two variants were not found in any of the other patients and controls. Our results suggest that three screened NEDD4-2 variants do not play a leading role in the pathogenesis of photosensitive epilepsy in the Turkish population.

Bromodomain-containing protein 2 gene in photosensitive epilepsy.

PURPOSE: Photosensitive epilepsy (PSE) is a form of reflex epilepsy characterized by seizures triggered by light. Genetic factors play an important role and some studies have indicated a possible role of the bromodomain-containing protein 2 (BRD2) gene. Our aim was to investigate the relationship between PSE and mutations of the BRD2 gene. METHODS: Fifty-four PSE patients with normal findings on neurological examination and neuro-imaging studies were included. All had a clear photoparoxysmal response in the EEG as reported by 2 experienced EEG interpreters. We investigated the BRD2 gene by denaturing high performance liquid chromatography followed by direct DNA sequencing. RESULTS: We failed to detect any mutations of the BRD2 gene. However, several single-nucleotide polymorphisms (SNPs) were observed in the gene; three of them were novel SNPs. The comparison of the patients showing these SNP changes with the remaining patients suggested a link between carrier status and prognosis. CONCLUSION: Our study did not confirm the presence of the genetic variants previously found to link the BRD2 gene to the idiopathic form of photosensitive epilepsy. SNP changes of the BRD2 gene may be clinically relevant but these findings need to be verified by larger studies.

ABL gene kinase domain mutation scanning by denaturing high performance liquid chromatography sequencing method.

OBJECTIVE: Despite the efficacy of the BCR-ABL tyrosine kinase inhibitor imatinib, the development of resistance against imatinib has been observed. The most important mechanisms known to cause resistance are point mutations in the ABL tyrosine kinase and the ATP domain. This study describes the use of denaturing high performance liquid chromatography (dHPLC) as a method to screen for mutations of the ABL gene. METHODS: We used the dHPLC based assay for the screening of ABL point mutations. Forty chronic myeloid leukemia (CML) patients who showed resistance to imatinib were screened in parallel by dHPLC and direct sequencing. RESULTS: Nine of the 40 patients (23%) had mutations. CONCLUSION: dHPLC can be a useful method for pre-screening. Analyzing the mutations and monitoring (high-risk) patients can improve their prognosis and survival rate. dHPLC can potentially become a valuable tool for regular testing of patients in the future.