De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy
作者： Hirotomo Saitsu , Mitsuhiro Kato , Takeshi Mizuguchi , Keisuke Hamada , Hitoshi Osaka
DOI: 10.1038/NG.150
关键词:
摘要: Early infantile epileptic encephalopathy with suppression-burst (EIEE), also known as Ohtahara syndrome, is one of the most severe and earliest forms epilepsy. Using array-based comparative genomic hybridization, we found a de novo 2.0-Mb microdeletion at 9q33.3-q34.11 in girl EIEE. Mutation analysis candidate genes mapped to deletion revealed that four unrelated individuals EIEE had heterozygous missense mutations gene encoding syntaxin binding protein 1 (STXBP1). STXBP1 (also MUNC18-1) an evolutionally conserved neuronal Sec1/Munc-18 (SM) essential synaptic vesicle release several species. Circular dichroism melting experiments mutant form was significantly thermolabile compared wild type. Furthermore, impaired. These findings suggest haploinsufficiency causes
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