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

Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Nephrology
DOI: 10.1111/nep.70152
Author: L. Azouaou
Language: English
Subfield: Nephrology
Field: Medicine
Open Access status: bronze
OpenAlex ID: W4416890965
FWCI:
Cites: 18
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