Conprehensive analysis of SCN1A noncoding region for epileptic disorders

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We investigated the noncoding regions of the SCN1A gene for 237 patients with Dravet syndrome and its related disorders who did not show any SCN1A mutations by sequence analysis of all coding exons and exon-intron boundaries. We invented Multiplex ligation-dependent probe amplification (MLPA) assays with probes for the 5'non-coding exons, their upstream and downstream regions of SCN1A. Among 237 patients, we found two patients with mosaic microdeletion removing the entire coding exons and boundary regions. We validated the mosaicism by subsequent array CGH and FISH. We also identified seven patients with deletions involving the coding region. One patient Dravet syndrome also showed a possible deletion in the 5'noncoding region which is detected by MLPA only. This study provides the first case of mosaic microdeletion involving the SCN1A region, and indicates the critical involvement of this mosaic microdeletion in the molecular pathology of Dravet syndrome.