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)t...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.展开更多
基金This cohort study is funded by the China National Natural Science Foundation(No.81970618)China National Clinical Research Centre Foundation(No.NCRC-2019-GP-02)+2 种基金Chongqing Science and Technology Commission project(No.cstc2016jcyjA0440)Chongqing Science and Technology plan project of Yuzhong District(No.2017045),Science and Technology Research Project of Chongqing Education Commission(No.KJZD-M201900401)the central government directs special funds for local science and technology development.
文摘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.
