Rapidly progressive pediatric fibronectin glomerulopathy driven by a novel FN1 mutation (p.Thr1917del): implications for early diagnosis and recognition of systemic involvement.

BACKGROUND

This study characterizes a pediatric case of fibronectin glomerulopathy (FNG) 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 FNG in February 2017 based on kidney biopsy and genetic testing at our institution. Clinical data and genetic reports were retrospectively analyzed. Fibronectin immunohistochemistry was performed on both kidney and gastric mucosal biopsy specimens. In addition, a literature review of Chinese and English databases was conducted to summarize genetically confirmed FNG cases.

RESULTS

The patient was a 9-year-old girl who presented with nephrotic-range proteinuria, microscopic hematuria, hypertension, and progressive kidney decline, culminating in kidney failure ten years after onset. Initial kidney 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. The comprehensive literature review of 72 patients revealed that the heparin-binding domain is a mutational hotspot, a finding consistent with the variant location in our case. The review also summarized disease management, progression, and post-transplant recurrence risk.

CONCLUSION

This study presents the first reported pediatric FNG case internationally associated with the FN1 p.Thr1917del mutation and offers histological evidence suggestive of a possible 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.