Identification of Nephrin gene variants in Indian children associated with Steroid sensitive and Steroid resistant nephrotic syndrome

Abstract

Nephrotic syndrome (NS) remains the most frequent indication of glomerular disease in childhood. The NPHS1 gene encoding nephrin protein is one of the common mutant genes in SRNS (Steroid Resistant Nephrotic syndrome) patients. These gene mutations are more likely to progress into ESKD (end-stage kidney disease). In the present study, we investigated the pathogenesis of the NPHS1 gene in Indian patients with SSNS and SRNS. Ninety-six children have been involved in the present study in which 37 belong to Steroid Sensitive Nephrotic syndrome (SSNS), 27 belong to Steroid Resistant Nephrotic syndrome (SRNS) 32 are healthy individuals. We designed a panel of NPHS1 gene (CDS- Coding sequence) and performed Illumina sequencing (MiSeq). We found a total of 45 variants in the NPHS1 gene. In addition, we found novel pathogenic c.2441A > G and two likely pathogenic missense variants, p.Gly395Ser, p.Ser400Pro in SSNS and SRNS patients by ACMG criteria. Therefore, early diagnosis of steroid resistant nephrotic syndrome in the Indian population can be made by identifying genetic variants using a customized gene panel.