UASSIGNED:作为雷帕霉素途径机制中GATOR1蛋白复合物的组装因子之一,NPRL3在癫痫的发病机制中起着重要作用。然而,NPRL3相关癫痫患者基因型和临床表型之间的相关性尚未明确.
UnASSIGNED:通过全外显子组测序(WES)确定了11例NPRL3相关癫痫患儿。临床表现的数据,实验室数据,脑成像发现,遗传结果,收集治疗方法。收集所有先前报告的NPRL3相关癫痫病例,并通过PubMed搜索进行审查。
未经评估:在11个孩子中,八个没有报告,其中2例表现为NPRL3相关癫痫的新表型。此外,WES鉴定出五个移码突变,三个无意义的突变,两个错义突变,和一个外显子删除。基于生物信息学分析,发现两个错义突变位点高度保守,和NPRL3基因的c.400G>A突变位点引起蛋白质结构的改变。迄今为止,已报告88名患者患有NPRL3相关缺陷,包括我们的11个案子.最常见的表现是睡眠相关的运动过度癫痫(SHE),额叶癫痫(FLE),颞叶癫痫.大多数患者(70%)的神经影像学检查结果正常,局灶性皮质发育不良是最常见的神经影像学异常(62.5%)。在NPRL3基因突变中,功能丧失(无意义突变,移码突变,和外显子缺失)是最常见的遗传变异(75%)。对于73%的NPRL3相关癫痫患者,钠通道阻滞剂单药治疗有效.手术对75%的神经影像学异常儿童有效。两例对手术或抗癫痫药物无反应的病例接受了生酮饮食(KD)治疗,这是有效的。1例癫痫早期用雷帕霉素治疗,这也是有效的。
UNASSIGNED:NPRL3相关癫痫具有很高的临床和遗传异质性。SHE和FLE是最常见的临床表现。此外,ISs是NPRL3相关癫痫的新表型,而变体c.275G>A,c.745G>A,和c.1270C>T可能是最常见的NPRL3基因突变。钠通道阻滞剂,手术,KD,雷帕霉素可能是这些患者的潜在治疗方法。我们的研究扩展了NPRL3相关癫痫的临床和遗传谱,为患者的精确治疗提供了重要信息。
UNASSIGNED: As one of the assembly factors of the GATOR1 protein complex in the mechanism of rapamycin pathway,
NPRL3 plays an important role in the pathogenesis of epilepsy. However, the correlation between genotype and clinical phenotype in patients with
NPRL3-related epilepsy has not been clarified.
UNASSIGNED: A total of 11 Chinese children with NPRL3-related epilepsy were identified through whole-exome sequencing (WES). The data from the clinical presentation, laboratory data, brain imaging findings, genetic results, and treatment methods were collected. All previously reported cases with NPRL3-related epilepsy were collected and reviewed through PubMed search.
UNASSIGNED: Among the 11 children, eight have not been reported, and two of them presented infantile spasms (ISs) as a new phenotype of NPRL3-related epilepsy. In addition, WES identified five frameshift mutations, three nonsense mutations, two missense mutations, and one exon deletion. Based on bioinformatics analysis, it was found that two missense mutation sites were highly conserved, and the c.400G>A mutation site of the NPRL3 gene caused the alteration of the protein structure. To date, 88 patients have been reported with
NPRL3-related defects, including our 11 cases. The most common presentations were sleep-related hypermotor epilepsy (SHE), frontal lobe epilepsy (FLE), and temporal lobe epilepsy. A majority of patients (70%) presented normal neuroimaging results, and focal cortical dysplasia was the most common neuroimaging abnormality (62.5%). Among the NPRL3 gene mutations, loss of function (nonsense mutations, frameshift mutations, and exons deletion) was the most common genetic variation (75%). For 73% of patients with NPRL3-related epilepsy, monotherapy of sodium channel blockers was effective. Surgery was effective for 75% of children with neuroimaging abnormalities. Two cases unresponsive to surgery or anti-seizure medications were treated with ketogenic diets (KD), which were effective. One case was treated with rapamycin at an early stage of epilepsy, which was effective as well.
UNASSIGNED: NPRL3-related epilepsy has high clinical and genetic heterogeneity. SHE and FLE are the most common clinical presentations. Furthermore, ISs are the new phenotypes of NPRL3-related epilepsy, while the variants c.275G>A, c.745G>A, and c.1270C>T may be the most common
NPRL3 gene mutations. Sodium channel blockers, surgery, KD, and rapamycin may be the potential treatments for these patients. Our study expanded the clinical and genetic spectrum of NPRL3-related epilepsy and provided important information for the precise treatment of patients.