PDF(Pubmed)
Abstract：
NPRL2 (nitrogen permease regulator like 2) is a component of the GATOR1(GAP activity towards rags complex 1) proteins, which is an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). However, FFEVF caused by NPRL2 variants has not been widely explored. Here, we describe a variant, 339+2T>C, in NPRL2 identified by trio whole-exome sequencing (WES) in a family. This splicing variant that occurred at the 5\' end of exon 3 was confirmed by minigene assays, which affected alternative splicing and led to exon 3 skipping in NPRL2. Our cases presented multiple seizure types (febrile seizures, infantile spasms, focal seizures, or focal to generalized tonic-clonic seizures). Electroencephalogram (EEG) showed frequent discharges in the left frontal and central regions. A favorable prognosis was achieved in response to vitamin B6 and topiramate when the patient was seven months old. Our study expands the phenotype and genotype spectrum of FFEVF and provides solid diagnostic evidence for FFEVF.
摘要：
NPRL2（类似2的氮通透酶调节剂）是GATOR1（对碎布复合物1的GAP活性）蛋白质的组成部分，它是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。然而,由NPRL2变体引起的FFEVF尚未被广泛探索。这里,我们描述了一个变体，339+2T>C,在一个家族中通过三重全外显子组测序（WES）鉴定的NPRL2中。这种发生在外显子3的5'末端的剪接变体通过小基因测定得到证实，这影响了选择性剪接并导致NPRL2中外显子3的跳跃。我们的病例表现为多种癫痫发作类型（高热惊厥，婴儿痉挛,局灶性癫痫发作,或局灶性全身强直阵挛性癫痫发作)。脑电图（EEG）显示左额叶和中央区频繁放电。患者7个月大时，对维生素B6和托吡酯的反应预后良好。我们的研究扩展了FFEVF的表型和基因型谱，并为FFEVF提供了坚实的诊断证据。
