Biallelic pathogenic variants in FLNB are associated with paediatric steroid-resistant nephrotic syndrome via podocyte cytoskeletal dysfunction

Biallelic FLNB (filamin B) variants, podocyte cytoskeletal dysfunction, impaired slit diaphragm integrity

Whole-exome sequencing of a pediatric steroid-resistant nephrotic syndrome (SRNS) cohort identifies biallelic pathogenic variants in FLNB in 3 probands. FLNB encodes filamin B, a cytoskeletal protein expressed in podocytes whose disruption impairs podocyte architecture. Functional studies demonstrate actin disorganization and impaired slit diaphragm integrity. This princeps publication establishes FLNB as a new SRNS gene in children, expanding the repertoire of podocyte cytoskeletal genes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

SRNS remains a leading cause of end-stage kidney disease in children with a major but still incomplete genetic basis. Identification of FLNB expands the spectrum of podocyte cytoskeletal genes (ACTN4, INF2, MYO1E) with direct impact on genetic workup in pediatric nephrology and steroid retreatment decisions.

Clinical impact: 3/3 · Evidence strength: 3/3 · Novelty: 2/2 · Sample size: 0/1 · Publication status: 1/1 → Total: 9/10