Identification of monogenic variants in steroid-resistant and steroid-sensitive nephrotic syndrome.

Pathogenic/likely pathogenic variants in known SRNS genes or phenocopy genes, WES diagnostic yield stratified by clinical criteria

237 families (183 SRNS, 54 SSNS/SDNS) underwent exome sequencing. A pathogenic variant in a known SRNS gene was identified in 15.8% of patients, with 3.3% additional carrying variants in phenocopy genes. Yield was significantly higher in patients with ≥50 Mb of homozygosity (44.7%) and disease onset before 1 year (41.9%). SSNS/SDNS is very rarely monogenic (1 case in 54).

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These data clarify criteria for prioritizing WES in pediatric SRNS: consanguinity and early onset are the two most robust predictive factors. Identification of phenocopy genes (3.3%) is an important clinical point — these patients have a different management than classical SRNS. A useful resource for geneticists collaborating with pediatric nephrology teams.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 6/10