Conprehensive analysis of SCN1A noncoding region for epileptic disorders

我们通过对所有编码外显子和外显子-内含子边界的序列分析，研究了237例未显示任何SCN1A突变的Dravet综合征及其相关疾病患者的SCN1A基因非编码区。我们发明了多重连接依赖探针扩增（Multiplex lig- dependent probe amplification， MLPA）方法，利用探针检测SCN1A的5'非编码外显子及其上游和下游区域。在237例患者中，我们发现有2例患者出现了马赛克微缺失，整个编码外显子和边界区域被移除。我们通过随后的阵列CGH和FISH验证了嵌合性。我们还发现了7例涉及编码区缺失的患者。1例Dravet综合征患者也表现出仅用MLPA检测到的5'非编码区可能缺失。本研究提供了首例涉及SCN1A区域的嵌合微缺失，并指出这种嵌合微缺失在Dravet综合征的分子病理中起着关键作用。

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.