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.

NPRL2（氮通透酶调节剂 2）是 GATOR1（GAP 对 rags 复合物 1 的活性）蛋白的一个组成部分，它是 mTORC1 通路的氨基酸感应分支的抑制剂。据报道，GATOR1 复杂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变异引起的FFEVF尚未得到广泛研究。在这里，我们描述了NPRL2中的一个变体，339+2T>C，它是由一个家族中的三重全外显子组测序 (WES) 鉴定的。这种发生在外显子 3 5' 末端的剪接变异被小基因检测证实，这影响了选择性剪接并导致NPRL2中的外显子 3 跳跃. 我们的病例呈现出多种癫痫发作类型（高热惊厥、婴儿痉挛、局灶性癫痫发作或局灶性至全身强直-阵挛性癫痫发作）。脑电图 (EEG) 显示左侧额叶和中央区域频繁放电。当患者 7 个月大时，对维生素 B6 和托吡酯的反应获得了良好的预后。我们的研究扩展了 FFEVF 的表型和基因型谱，并为 FFEVF 提供了可靠的诊断证据。