Zhu Xiujuan, Zhang Yanqin, Yu Zihua, Yu Li, Huang Wenyan, Sun Shuzhen, Li Yingjie, Wang Mo, Li Yongzhen, Sun Liangzhong, Yang Qing, Deng Fang, Shao Xiaoshan, Liu Ling, Liu Cuihua, Qin Yuanhan, Feng Shipin, Zhu Hongtao, Yang Fang, Zheng Weimin, Zheng Wanqi, Zhong Rirong, Hou Ling, Mao Jianhua, Wang Fang, Ding Jie
Department of Nephrology, The Children Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Front Med (Lausanne). 2022 Jun 9;9:885178. doi: 10.3389/fmed.2022.885178. eCollection 2022.
Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage kidney disease (ESKD) in children and young adults. For approximately 30% of children with SRNS results from a genetic cause. In this study, genotype-phenotype correlations in a cohort of 283 pediatric patients with SRNS or early-onset NS (nephrotic syndrome presenting within the first year of life) from 23 major pediatric nephrology centers in China were analyzed. All patients were performed with next-generation sequencing and Sanger sequencing. The overall mutation detection rate was 37.5% (106 of 283 patients). WT1 was the most frequently detected mutation, followed by NPHS1, NPHS2, and ADCK4, and these four major causative genes (WT1, NPHS1, NPHS2, and ADCK4) account for 73.6% of patients with monogenic SRNS. Thirteen of 106 individuals (12.3%) carried mutations in ADCK4 that function within the coenzyme Q10 biosynthesis pathway. In the higher frequently ADCK4-related SRNS, two mutations, c.737G>A (p.S246N) and c.748G>C (p.D250H), were the most prevalent. Our study provides not only definitive diagnosis but also facilitate available targeted treatment for SRNS, and prediction of prognosis and renal outcome. Our indications for genetic testing are patients with FSGS, initial SRNS, cases of positive family history or those with extra-renal manifestations.
激素抵抗型肾病综合征（SRNS）是儿童和青年终末期肾病（ESKD）的主要病因之一。约30%的儿童SRNS由遗传因素引起。本研究分析了来自中国23个主要儿科肾脏病中心的283例SRNS或早发性肾病综合征（肾病综合征在出生后第一年内出现）儿科患者队列中的基因型-表型相关性。所有患者均进行了二代测序和桑格测序。总体突变检出率为37.5%（283例患者中的106例）。WT1是最常检测到的突变基因，其次是NPHS1、NPHS2和ADCK4，这四个主要致病基因（WT1、NPHS1、NPHS2和ADCK4）占单基因SRNS患者的73.6%。106例个体中有13例（12.3%）携带ADCK4突变，该基因在辅酶Q10生物合成途径中发挥作用。在ADCK4相关SRNS发生率较高的情况下，两个突变c.737G>A（p.S246N）和c.748G>C（p.D250H）最为常见。我们的研究不仅为SRNS提供了明确的诊断，还便于进行有效的靶向治疗，并预测预后和肾脏结局。我们进行基因检测的指征是局灶节段性肾小球硬化（FSGS）患者、初发SRNS患者、有阳性家族史的病例或有肾外表现的患者。
