关键词: SCN1A, 癫痫, 启动子, 突变, 保守性

Abstract: Objective To screen and analyze the mutations of SCN1A promoter regions from the patients with Dravet syndrome and to evaluate the relationship between mutation and disease. Methods Peripheral blood of 24 patients with Dravet syndrome and 100 unrelated normal persons were collected and genomic DNA was extracted. PCR and sequencing of SCN1A promoter region were then performed. To evaluate the possibility of mutation inducing disease, bioinformatics analysis was applied to analyze the conservation of the sequences including the mutation sites and predict the potential transcriptional elements. Results Two mutations -244 C>T and -662 G>- were identified from patients and both mutations were found in their farther genomic DNA, but not in unrelated normal persons. The nucleotide sites -244 and -662 were highly conserved in mammals (100%). The average nucleotide identity rate of -244 adjacent sequences (20 bp upstream and downstream of the mutation sites) between human and other species was 90%, and was only 60% for that of -662. Potential transcription regulatory elements and factors were found on the sequence including -244, but not on the sequence including -662. Conclusions The two mutations may be associated with Dravet syndrome and further studied should be performed to demonstrate their pathogenic mechanisms.

Key words: SCN1A, epilepsy, promoter, mutation, conservation