Yang Dongling, Wang Jinqiu, Qin Zailong, Feng Juntan, Mao Chengyun, Chen Yuyi, Huang Xuelin, Ruan Yiyan
Ruikang Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, China.
Department of Pediatric Neurology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, China.
Epilepsia Open. 2024 Feb;9(1):33-40. doi: 10.1002/epi4.12856. Epub 2023 Nov 28.
Nitrogen permease regulator-like 3 (NPRL3) has been reported to play a role in seizure onset. The principal manifestation of NPRL3-related epilepsy is a range of epilepsy-associated syndromes, such as familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), and temporal lobe epilepsy (TLE). The association between phenotype and genotype of NPRL3 mutations remains inadequately described. This study aimed to explore the phenotypic and genotypic spectra of NPRL3-related epilepsy. We reported two novel NPRL3 variants in two unrelated epilepsy cases, including a nonsense (c.1174C > T, p.Gln392*) and a missense variant (c.1322C > T, p.Thr441Met). Following a review of the literature, a total of 116 cases of NPRL3-related epilepsy were assessed, mostly with nonsense and frameshift mutations. Our findings suggest that patients harboring various NPRL3 variants exhibit variable clinical manifestations. In addition, it may be worthwhile to consider the NPRL3 mutations in epilepsy patients with a family history. This study provides useful information for the treatment and prognosis by expanding the phenotypic and genotypic spectrum of NPRL3-related epilepsy. PLAIN LANGUAGE SUMMARY: This study expands the phenotypic and genotypic spectra of NPRL3-related epilepsy by reporting two cases with different novel variants. Following a review of the literature, it was observed that patients harboring various NPRL3 variants exhibited a variability of clinical manifestations. Also, patients carrying nonsense mutations are frequently prone to drug resistance and other severe comorbidities such as developmental delay, but more cases need to be collected to confirm these findings.
据报道，氮通透酶调节因子样3（NPRL3）在癫痫发作中起作用。NPRL3相关癫痫的主要表现是一系列与癫痫相关的综合征，如具有可变病灶的家族性局灶性癫痫（FFEVF）、睡眠相关的运动过多性癫痫（SHE）和颞叶癫痫（TLE）。NPRL3突变的表型与基因型之间的关联仍未得到充分描述。本研究旨在探索NPRL3相关癫痫的表型和基因型谱。我们在两例无关的癫痫病例中报告了两个新的NPRL3变体，包括一个无义突变（c.1174C>T，p.Gln392*）和一个错义变体（c.1322C>T，p.Thr441Met）。在回顾文献后，共评估了116例NPRL3相关癫痫病例，大多数为无义突变和移码突变。我们的研究结果表明，携带各种NPRL3变体的患者表现出不同的临床表现。此外，对于有家族史的癫痫患者，考虑NPRL3突变可能是值得的。本研究通过扩大NPRL3相关癫痫的表型和基因型谱，为治疗和预后提供了有用信息。通俗易懂的总结：本研究通过报告两例具有不同新变体的病例，扩大了NPRL3相关癫痫的表型和基因型谱。在回顾文献后发现，携带各种NPRL3变体的患者临床表现存在差异。此外，携带无义突变的患者经常容易出现耐药性和其他严重合并症，如发育迟缓，但需要收集更多病例来证实这些发现。
