Pathogenic variants in COL4A3, COL4A4, JAG1, and NPHS2 genes in focal segmental glomerulosclerosis: Insights from targeted gene panel sequencing.

Background: Monogenic causes of focal segmental glomerulosclerosis (FSGS) are increasingly recognized, but data from highly consanguineous Middle Eastern populations remain limited. This study explored the diagnostic yield and descriptive genotype-phenotype correlations of a targeted gene panel in Iraqi patients with biopsy-proven FSGS from a cohort enriched for familial, early-onset, and consanguineous disease. Methods: Thirty consecutive patients with histologically confirmed FSGS underwent next-generation sequencing using a 98-gene renal disease panel. Variants were classified according to ACMG guidelines and interpreted with clinical and histopathological findings. Exploratory analyses compared variant-positive and variant-negative patients and assessed simple clinical predictors of a positive genetic result. Results: Pathogenic variants were identified in 10 of 30 patients (33.3%) in COL4A3 ( Conclusions: In this predominantly familial and early-onset FSGS cohort, one-third of patients harbored pathogenic variants, supporting the value of gene-panel testing in selected young or syndromic patients while underscoring the need for validation in larger, more representative cohorts.