Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome

Jia Jiao; Li Wang; Fenfen Ni; Mo Wang; Shipin Feng; Xiaojie Gao; Han Chan; Xueying Yang; Hao Lee; Huan Chi; Xuelan Chen; Daoqi Wu; Gaofu Zhang; Baohui Yang; Anshuo Wang; Qin Yang; Junli Wan; Sijie Yu; Qiu Li

doi:10.1016/j.gendis.2022.03.023

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Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome

Full-length article | 更新时间：2022-11-09

- 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
- Genes & Diseases 2022年9卷第6期
- 作者机构：
  
  1. Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics,Chongqing,PR China,400015
  2. Department of Nephrology, Chengdu Women and Children Central Hospital,Sichuan,Chengdu,PR China,610091
  3. Department of Nephrology, Sheen Children's Hospital,Guangdong,Shenzhen,PR China,518034
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2022.03.023
  中图分类号：
- 纸质出版日期：2022，
  
  网络出版日期：2022-11-1，
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Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome[J]. Genes & Diseases, 2022,9(6).

Jia Jiao, Li Wang, Fenfen Ni, et al. Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome[J]. Genes & Diseases, 2022,9(6).
Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome[J]. Genes & Diseases, 2022,9(6). DOI： 10.1016/j.gendis.2022.03.023.

Jia Jiao, Li Wang, Fenfen Ni, et al. Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome[J]. Genes & Diseases, 2022,9(6). DOI： 10.1016/j.gendis.2022.03.023.

摘要

Abstract

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.

关键词

Keywords

Clinical phenotypesGenetic phenotypesMulticenter cohortNephrotic syndromePediatricWhole-exome sequencing

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