Genetic analysis of Indian patients with steroid-resistant nephrotic syndrome in children

Abstract

Abstract Introduction: Steroid-resistant nephrotic syndrome (SRNS) children carry poor outcomes. In the hope of achieving remission, patients are frequently treated with repeated courses of steroids and other immunosuppressives. Patients with genetic mutations are usually steroid-resistant, except for a few patients. There is a paucity of data on genetic mutations in Indian children with SRNS. Methods: In this study, we identified SRNS patients and were asked for whole exome sequencing to identify mutations responsible for steroid resistance after informed consent from the parents or Guardians. We also analyzed the phenotypic and genotypic association with clinical course and response to varied immunosuppressive medications. Result: A total of 82 SRNS children included in the study were categorized into syndromic, in whom systemic features other than NS were also present; and non-syndromic SRNS do not have any other systemic features. Of the 82 patients subjected to genetic analysis, 29 did not reveal any mutations, and 53 showed genetic mutations. Genetic mutation variants were categorized according to ACMG criteria which showed 10 pathogenic, 5 likely pathogenic, and 38 variants of unknown significance. Mutations detected in SRNS children differed from those reported in the Western world. Nineteen of 82 SRNS children had Alport syndrome on mutational analysis. We identified many novel mutations associated with SNRS and also observed that many mutations were responsive to immunosuppression. Conclusions: The genetic analysis may obviate the need for a repeated course of immunosuppression with obvious mutations that are unlikely to respond to immunosuppression. Alport syndrome may present as SRNS in children.