Rapidly Progressive Pediatric Fibronectin Glomerulopathy Driven by a Novel FN1 Mutation (p.Thr1917del): Implications for Early Diagnosis and Recognition of Systemic Involvement

Objective This study characterizes a pediatric case of glomerulopathy with fibronectin deposits (GFND) caused by a novel FN1 variant and investigates the evidence for systemic involvement and genotype-phenotype correlations through a comprehensive literature review. Methods We report a female child diagnosed with GFND in February 2017 based on renal biopsy and genetic testing at our institution. Clinical data and genetic reports were retrospectively analyzed. Fibronectin immunohistochemistry was performed on both renal and gastric mucosal biopsy specimens. In addition, a systematic review of Chinese and English databases was conducted to summarize genetically confirmed GFND cases. Results The patient was a 9-year-old girl who presented with nephrotic-range proteinuria, microscopic hematuria, hypertension, and progressive renal decline, culminating in end-stage renal disease (ESRD) eight years after onset. Initial renal pathology suggested atypical membranoproliferative glomerulonephritis (MPGN). Genetic analysis identified a novel de novo heterozygous deletion in the FN1 gene (NM_212482.5: c.5749_5751delACT; p.Thr1917del). Gastric mucosal immunohistochemistry revealed specific fibronectin deposition within the extracellular matrix, indicating systemic involvement. Literature review of 72 patients identified the heparin-binding domain as the main mutational hotspot and summarized disease management, progression, and post-transplant recurrence risk. Conclusion This study presents the first reported pediatric GFND case internationally associated with the FN1 p.Thr1917del mutation and offers histological evidence supporting its classification as a systemic extracellular matrix proteinopathy. Our findings underscore the value of fibronectin staining and FN1 genetic testing in patients with atypical MPGN and broaden the disease's clinical and genetic profile.