A Novel Pattern of Mutations in Northern Indian Children with Steroid-Resistant Nephrotic Syndrome

Background: Steroid Resistant Nephrotic Syndrome(SRNS) in children poses treatment challenges, and many had genetic mutations. Data on genetics is scarce. Methods: A prospective study(Oct2018–April2023) enrolled children with SRNS who consented to DNA isolation and next-generation sequencing to explore genetic variants and their clinical outcomes. Clinical, histological and genetic data were recorded. Results: Out of 680 NS patients,121(17.8%) had SRNS and 96consented to genetic analysis. Of them 69(71.9%) were early SRNS and 27(28.1%) late nonreponder. 63(65.7%) had reportable genetic variants and genetic variant Pathogenic or likely Pathogeneic is shown in Image1, and genetic variant Variant of Unknown Significance or likely benign in Image 2. COL4A genes mutation was seen in 20(31.7%)patients. Renal biopsy showed FSGS in 31/42(74%) with variants. Complete(11%)and Partial remission(23.9%) with CNI was observed. Conclusion: 65.7% SRNS patients had genetic variants,and COL4A variants were responsible for 31.7 %. CNI reponse was also observed. Funding: Government Support – Non-U.S.Genetic profile of patients with genetic variant classified as Pathogenic(P) or likely Pathogeneic (LP)Genetic profile of patients with genetic variant classified as Variant of Unknown Significance (VUS) or likely benign (LB)