PDF(Pubmed)
Abstract：
UNASSIGNED: Disheveled, EGL-10, and pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a component of GTPase-activating protein (GAP) activity toward the RAG complex 1 (GATOR1) protein, which is an inhibitor of the amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). With the wide application of whole exome sequencing (WES), more and more variations in DEPDC5 were uncovered in FFEVF families.
UNASSIGNED: A family with a proband diagnosed with familial focal epilepsy with variable foci (FFEVF) was involved in this study. Whole exome sequencing (WES) was performed in the proband, and Sanger sequencing was used to confirm the variation carrying status of the family members. Mini-gene splicing assay was performed to validate the effect on the alternative splicing of the variation.
UNASSIGNED: A novel variant, c.1217 + 2T>A, in DEPDC5 was identified by WES in the proband. This splicing variant that occurred at the 5\' end of intron 17 was confirmed by mini-gene splicing assays, which impacted alternative splicing and led to the inclusion of an intron fragment. The analysis of the transcribed mRNA sequence indicates that the translation of the protein is terminated prematurely, which is very likely to result in the loss of function of the protein and lead to the occurrence of FFEVF.
UNASSIGNED: The results suggest that c.1217 + 2T>A variations in DEPDC5 might be the genetic etiology for FFEVF in this pedigree. This finding expands the genotype spectrum of FFEVF and provides new etiological information for FFEVF.
UNASSIGNED: A family with a proband diagnosed with familial focal epilepsy with variable foci (FFEVF) was involved in this study. Whole exome sequencing (WES) was performed in the proband, and Sanger sequencing was used to confirm the variation carrying status of the family members. Mini-gene splicing assay was performed to validate the effect on the alternative splicing of the variation.
UNASSIGNED: A novel variant, c.1217 + 2T>A, in DEPDC5 was identified by WES in the proband. This splicing variant that occurred at the 5\' end of intron 17 was confirmed by mini-gene splicing assays, which impacted alternative splicing and led to the inclusion of an intron fragment. The analysis of the transcribed mRNA sequence indicates that the translation of the protein is terminated prematurely, which is very likely to result in the loss of function of the protein and lead to the occurrence of FFEVF.
UNASSIGNED: The results suggest that c.1217 + 2T>A variations in DEPDC5 might be the genetic etiology for FFEVF in this pedigree. This finding expands the genotype spectrum of FFEVF and provides new etiological information for FFEVF.
摘要：
■不规则,EGL-10和含pleckstrin（DEP）结构域的蛋白5（DEPDC5）是GTP酶激活蛋白（GAP）对RAG复合物1（GATOR1）蛋白活性的组成部分，它是哺乳动物雷帕霉素复合物1（mTORC1）途径的氨基酸传感分支的抑制剂。据报道，GATOR1复合物变异与具有可变病灶的家族性局灶性癫痫（FFEVF）相关。随着全外显子组测序(WES)技术的广泛应用,在FFEVF家族中发现了越来越多的DEPDC5变异。
■本研究涉及一个被诊断为家族性局灶性癫痫（FFEVF）的先证者家庭。在先证中进行全外显子组测序（WES），Sanger测序用于确认家庭成员的变异携带状态。进行小基因剪接测定以验证对变异的选择性剪接的影响。
■一种新颖的变体，c.1217+2T>A，DEPDC5在先证者中由WES鉴定。这种发生在内含子17的5'末端的剪接变体通过小基因剪接测定得到证实，这影响了可变剪接并导致包含内含子片段。对转录的mRNA序列的分析表明，蛋白质的翻译过早终止，这很可能导致蛋白质功能的丧失并导致FFEVF的发生。
■结果表明，DEPDC5的c.1217+2T>A变异可能是该谱系中FFEVF的遗传病因。这一发现扩展了FFEVF的基因型谱，并为FFEVF提供了新的病因信息。
■本研究涉及一个被诊断为家族性局灶性癫痫（FFEVF）的先证者家庭。在先证中进行全外显子组测序（WES），Sanger测序用于确认家庭成员的变异携带状态。进行小基因剪接测定以验证对变异的选择性剪接的影响。
■一种新颖的变体，c.1217+2T>A，DEPDC5在先证者中由WES鉴定。这种发生在内含子17的5'末端的剪接变体通过小基因剪接测定得到证实，这影响了可变剪接并导致包含内含子片段。对转录的mRNA序列的分析表明，蛋白质的翻译过早终止，这很可能导致蛋白质功能的丧失并导致FFEVF的发生。
■结果表明，DEPDC5的c.1217+2T>A变异可能是该谱系中FFEVF的遗传病因。这一发现扩展了FFEVF的基因型谱，并为FFEVF提供了新的病因信息。
