Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome.
Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome.
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多中心队列的全外观测序确定了与小儿肾病综合征中临床表型相关的遗传变化。
DOI：
10.1016/j.gendis.2022.03.023
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发表时间：
2022-11
期刊：
影响因子：
6.8
通讯作者：
Li, Qiu
中科院分区：
文献类型：
--
作者：
Jiao, Jia;Wang, Li;Ni, Fenfen;Wang, Mo;Feng, Shipin;Gao, Xiaojie;Chan, Han;Yang, Xueying;Lee, Hao;Chi, Huan;Chen, Xuelan;Wu, Daoqi;Zhang, Gaofu;Yang, Baohui;Wang, Anshuo;Yang, Qin;Wan, Junli;Yu, Sijie;Li, Xiaoqin;Wang, Mei;Chen, Xiaofeng;Mai, Xianying;Ruan, Xiongzhong;Yang, Haiping;Li, Qiu
了解不同病因的肾病综合征（NS）儿童的遗传和临床表型之间的关联对于早期临床指导至关重要。我们采用全外显子组测序（WES）检测637例患者的多中心队列中NS的单基因病因。在这项研究中，30.0%的特发性类固醇耐药肾病综合征（SRNS）患者的遗传原因被确定。除了先天性肾病综合征（CNS），单基因疾病的发病率没有显着差异的基础上，在表现的年龄。在39.5%的局灶节段性肾小球硬化（FSGS）患者和9.2%的微小病变（MCD）患者中检测到致病突变。就不同类型的类固醇耐药患者的模式而言，在34.8%的原发性耐药患者、2.9%的继发性耐药患者和71.4%的多药耐药儿童中确定了单基因突变。在各种强化免疫抑制治疗中，他克莫司（TAC）的反应率最高，49.7%的特发性SRNS患者达到完全缓解。单基因疾病的特发性SRNS患者表现出类似的多药耐药模式，只有31.4%的单基因疾病患者在TAC治疗后获得部分缓解。在平均4.1年的随访中，21.4%的单基因疾病特发性SRNS患者进展为终末期肾病（ESRD）。总的来说，这项研究提供的证据表明，基因检测是必要的假定类固醇耐药和特发性SRNS患者，特别是那些原发性和/或多药耐药。
Understanding the association between the genetic and clinical phenotypes in children with nephrotic syndrome (NS) of different etiologies is critical for early clinical guidance. We employed whole-exome sequencing (WES) to detect monogenic causes of NS in a multicenter cohort of 637 patients. In this study, a genetic cause was identified in 30.0% of the idiopathic steroid-resistant nephrotic syndrome (SRNS) patients. Other than congenital nephrotic syndrome (CNS), there were no significant differences in the incidence of monogenic diseases based on the age at manifestation. Causative mutations were detected in 39.5% of patients with focal segmental glomerulosclerosis (FSGS) and 9.2% of those with minimal change disease (MCD). In terms of the patterns in patients with different types of steroid resistance, a single gene mutation was identified in 34.8% of patients with primary resistance, 2.9% with secondary resistance, and 71.4% of children with multidrug resistance. Among the various intensified immunosuppressive therapies, tacrolimus (TAC) showed the highest response rate, with 49.7% of idiopathic SRNS patients achieving complete remission. Idiopathic SRNS patients with monogenic disease showed a similar multidrug resistance pattern, and only 31.4% of patients with monogenic disease achieved a partial remission on TAC. During an average 4.1-year follow-up, 21.4% of idiopathic SRNS patients with monogenic disease progressed to end-stage renal disease (ESRD). Collectively, this study provides evidence that genetic testing is necessary for presumed steroid-resistant and idiopathic SRNS patients, especially those with primary and/or multidrug resistance.
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影响因子：
5.5
作者：
通讯作者：
--
DOI：
10.2215/cjn.03060316
发表时间：
2016-11-01
影响因子：
9.8
作者：
Francis, Anna;Trnka, Peter;McTaggart, Steven J.
通讯作者：
McTaggart, Steven J.
影响因子：
13.6
作者：
Giglio, Sabrina;Provenzano, Aldesia;Romagnani, Paola
通讯作者：
Romagnani, Paola
影响因子：
19.6
作者：
Bullich, Gemma;Domingo-Gallego, Andrea;Ars, Elisabet
通讯作者：
Ars, Elisabet
影响因子：
13.6
作者：
Gbadegesin, Rasheed A.;Adeyemo, Adebowale;Winn, Michelle P.
通讯作者：
Winn, Michelle P.