Lv Qiu, Niu Yue, Xu Zhao, Qin Jiong, Yang Zhixian
Department of Pediatrics, Peking University People's Hospital, Beijing, China.
Epilepsy Center, Peking University People's Hospital, Beijing, China.
Front Neurol. 2024 Oct 1;15:1410187. doi: 10.3389/fneur.2024.1410187. eCollection 2024.
-related neuro-renal syndrome (NRS), caused by pathogenic variants of the gene, is characterized by epilepsy, developmental delay (DD) and renal disorders. The severity of the neurological effects as well as the presence of renal disorders is variable among patients. Here, we report three additional patients with clinical features compatible with NRS and summarize the association between the variants' loci and phenotype of -related NRS.
A retrospective analysis was conducted for three Chinese children with NRS due to variants identified through whole-exome sequencing (WES). Previous reports of patients with -related NRS were reviewed systematically. Demographic and clinical data were collected from these patients.
Two truncating variants in three NRS patients were identified in our study, including c.1327_c.1328delCCinsTG (p. Arg443*) and c.1375C>T (p.Gln459*). Our three patients all exhibited drug-resistant epilepsy and early-onset DD, and two of whom developed electrical status epilepticus during sleep (ESES). Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia in one patient and normal in the other two. All three patients demonstrated nephrotic range proteinuria (NRP) or nephrotic syndrome (NS) with normal renal function during follow-up. There was a total of 27 patients with -related NRS have been identified to date. The most common clinical features are renal diseases (89%), DD (89%), followed by epilepsy (78%). 67% of patients eventually progressed to end-stage renal disease (ESRD). Focal seizure was the most frequent seizure type (57%). 52% of patients presented drug-resistant epilepsy. 64% of patients exhibited non-specific brain MRI abnormalities. Brain atrophy was the most common change (50%). Two patients with TRIM8 variants closer to the N-terminal had neurological diseases without renal damage. Five patients with variants closer to the C-terminal had no severe neurological diseases. Seven patients had Gln459* variant which is the most common variant (7/27, 25.9%). The severity of the renal and neurological damage of the seven patients was variable.
This study expands the number of individuals with confirmed NRS due to pathogenic variants in . Neurological and renal phenotype with the same variant locus differed in their severity. Further research is needed to explore the relationship between genotype and phenotype of variants.
由 基因的致病变异引起的 -相关神经肾综合征（NRS），其特征为癫痫、发育迟缓（DD）和肾脏疾病。患者的神经学影响严重程度以及肾脏疾病的存在情况各不相同。在此，我们报告另外三名具有与NRS相符临床特征的患者，并总结变异位点与 -相关NRS表型之间的关联。
对通过全外显子组测序（WES）鉴定出因 变异而患有NRS的三名中国儿童进行回顾性分析。系统回顾了先前关于 -相关NRS患者的报告。收集这些患者的人口统计学和临床数据。
在我们的研究中，在三名NRS患者中鉴定出两个 截短变异，包括c.1327_c.1328delCCinsTG（p.Arg443*）和c.1375C>T（p.Gln459*）。我们的三名患者均表现出耐药性癫痫和早发性DD，其中两名在睡眠期间发生癫痫持续状态（ESES）。脑磁共振成像（MRI）显示一名患者有脑室周围白质软化，另外两名正常。所有三名患者在随访期间均表现出肾病范围蛋白尿（NRP）或肾病综合征（NS）且肾功能正常。迄今为止，总共已鉴定出27例与 -相关的NRS患者。最常见的临床特征是肾脏疾病（89%）、DD（89%），其次是癫痫（78%）。67%的患者最终进展为终末期肾病（ESRD）。局灶性发作是最常见的发作类型（57%）。52%的患者表现出耐药性癫痫。64%的患者表现出非特异性脑MRI异常。脑萎缩是最常见的变化（50%）。两名具有更靠近N端的TRIM8变异的患者患有神经疾病但无肾脏损害。五名具有更靠近C端的 变异的患者没有严重神经疾病。七名患者具有Gln459*变异，这是最常见的变异（7/27，25.9%）。这七名患者的肾脏和神经损害严重程度各不相同。
本研究扩大了因 致病变异而确诊为NRS的个体数量。具有相同变异位点的神经和肾脏表型在严重程度上有所不同。需要进一步研究以探索 变异的基因型与表型之间的关系。
