Clinicopathological features of familial fibronectin glomerulopathy caused by a splice site variant in the Fibronectin 1 gene: a case report.

Abstract

Fibronectin glomerulopathy (FNG) is a rare autosomal dominant inherited disease characterized by extensive deposits of fibronectin in the mesangium and subendothelial space of the glomeruli with membranoproliferative glomerulonephritis (MPGN)-like pattern. Currently, ten exonic and one intronic pathogenic variants in the fibronectin 1 gene have been identified; however, genotype-phenotype correlation data are lacking. We herein report a familial FNG caused by a splice site variant in intron 36 (c.5888-2A > G). The gene mutation was recently found, but to our knowledge, this is the first case report of a familial FNG with the intronic variant that describes the clinicopathological characteristics. In the current study, Case 1 is a previously healthy 29-year-old woman with nephrotic syndrome. Treatment with glucocorticoids, combined with the immunosuppressant mizoribine and an angiotensin II receptor blocker (ARB), resulted in an incomplete remission of nephrotic syndrome; however, renal function has been preserved. Case 2, the mother of Case 1, is a 49-year-old woman with vasculo-Behçet's disease with mild proteinuria and renal dysfunction. Due to the administration of azathioprine, aspirin, and ARB, renal function and proteinuria have been stable over 10 years. The kidney biopsy revealed MPGN-like histological features in both the mother and the daughter; however, the mesangial area exhibited a milder expansion in the mother than in the daughter. Accumulating genotype-phenotype correlation data will be essential for managing FNG.