High Diagnostic Yield of Genetic Screening in Autosomal Dominant Steroid‐Resistant Nephrotic Syndrome: Predominance of INF2 and TRPC6 and Identification of a Novel Gene

Aims To investigate the genetic architecture of autosomal dominant steroid‐resistant nephrotic syndrome (AD‐SRNS) in Algerian families and to evaluate the diagnostic yield of targeted next‐generation sequencing, with a particular focus on podocyte‐related genes and the identification of potential novel variants. Methods We studied 89 affected individuals from 32 unrelated Algerian families with suspected AD‐SRNS. Genetic testing was performed using a custom panel of 52 podocyte‐related genes, followed by segregation analysis when available. Clinical, histological, and transplant‐related data were retrospectively reviewed. Variants were interpreted according to ACMG guidelines, and genotype–phenotype correlations were analysed. Results Pathogenic or likely pathogenic variants were identified in 21 families (65.6%). The most frequently mutated genes were INF2 (51%) and TRPC6 (43%), followed by ACTN4 and WT1. A novel likely pathogenic variant in a candidate gene (XYZ1) was identified in one family. Mutation‐positive families showed earlier disease onset, a higher prevalence of FSGS, and more frequent progression to ESRD before age 30. Extrarenal features occurred in 20% of patients. Conclusion This study represents the first comprehensive genetic analysis of AD‐SRNS in North Africa, demonstrating a high diagnostic yield and expanding the AD‐SRNS spectrum through the identification of a novel gene candidate. These findings highlight the importance of integrating genomic testing into routine nephrology practice, particularly in underrepresented populations.