Novel insights in the genetics of steroid-sensitive nephrotic syndrome in childhood

Abstract

Steroid sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood and there is growing evidence that genetics play a role in the susceptibility for the disease. Familial clustering has been observed and led to several studies on familiar SSNS trying to identify a monogenic cause of the disease. Until now, however, none of these have provided convincing evidence for Mendelian inheritance. This and the phenotypic variability within SSNS suggest a complex inheritance pattern, where multiple variants, interactions between those and the environment play a role in disease development. Genome wide association studies (GWAS) have been used to investigate this complex disease. We herein highlight new insights in the genetics of the disease provided by GWAS and how these fit into our understanding of the pathogenesis of SSNS.

B-Cell Dysregulation in Idiopathic Nephrotic Syndrome: What We Know and What We Need to Discover

“…SSNS is a heterogeneous disorder and the different forms of the disease are likely to be mediated by a complex interplay between the environment, the glomerular permeability barrier and the immune system ( 5 ). Despite the lack of a monogenic cause of the disease, genetic variants predisposing to develop SSNS following environmental triggers are emerging, as recently reviewed ( 42 ). Among all the identified SSNS-associated genetic variants, the strongest association was found in the HLA region, as identified by exome array and transethnic genome-wide association studies in large pediatric cohorts ( 43 – 46 ), supporting the role of an immune dysregulation in the antigen presentation machinery in SSNS forms ( 44 ).…”

An updated view of the pathogenesis of steroid-sensitive nephrotic syndrome

“…However, such variants in a single causative gene account for only a few families in SSNS. Most SSNS cases are considered to be multifactorial, and several reports have clarified susceptibility genes in SSNS [49][50][51][52][53] (reviewed in [54]).…”

Therapeutic trials in difficult to treat steroid sensitive nephrotic syndrome: challenges and future directions

“…Pathogenesis of nephrotic syndrome is not fully understood and likely results from complex interactions between genetic, immune, and environmental factors. Detailed reviews of SSNS pathogenesis [9] and SSNS genetics were recently published [10]. Human leukocyte antigen (HLA) risk alleles and mutations in immune regulatory genes increase the risk of SSNS but appear insufficient to cause disease alone.…”