Autosomal dominant focal segmental glomerulosclerosis by INF2 p.Arg218Trp and p.Ser186Pro mutations: three case reports and literature review.

backgroundFocal segmental glomerulosclerosis(FSGS) is a histologic lesion of podocyte injury with diverse etiologies including mutations in the inverted formin-2 gene(INF2), which belongs to the formin family and regulates actin cytoskeleton-dependent cellular processes. CASE PRESENTATION: We report two cases of INF2 p.Arg218Trp and one case of p.Ser186Pro, all exhibiting an autosomal dominant(AD) inheritance pattern. The clinical presentations of the two patients with INF2 p.Arg218Trp varied widely. One patient, diagnosed with proteinuria in adolescence, maintained normal renal function, while the other experienced a youthful onset followed by rapid progression to end-stage renal disease (ESRD) and required hemodialysis treatment. The patient with p.Ser186Pro also had an early onset, with renal biopsy revealing progression from minimal change disease (MCD) to FSGS, leading to ESRD and necessitating hemodialysis treatment.

conclusionsThese cases add to the clinical spectrum associated with INF2-related FSGS and underscore the importance of genetic evaluation in patients with early-onset or familial kidney disease. They show considerable intrafamilial and interfamilial variability in penetrance and expressivity, highlighting the complexity of genotype-phenotype correlations. Genetic screening and family counseling remain essential in suspected hereditary FSGS. Further studies are warranted to clarify the molecular mechanisms and guide management strategies.