Peer-reviewed article
Rapidly progressive pediatric fibronectin glomerulopathy driven by a novel FN1 mutation (p.Thr1917del): implications for early diagnosis and recognition of systemic involvement.
Xiaobin Chen, Jun Huang, Yi Chen, Yunfan Zhang, Jinfeng Lin et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a medical case report describing a single pediatric patient with fibronectin glomerulopathy, a rare genetic kidney disease. The report documents the patient's clinical presentation, genetic mutation, and systemic involvement through tissue analysis. While the study involves a child, it focuses on clinical diagnosis and disease characterization rather than child well-being, health interventions, or policy relevant to the African Institute for Children Studies.
Key points
- Novel de novo FN1 gene deletion (p.Thr1917del) identified in a 9-year-old girl with progressive kidney disease
- Patient presented with nephrotic-range proteinuria, microscopic hematuria, and hypertension, progressing to kidney failure over ten years
- Gastric mucosal biopsy showed fibronectin deposition, suggesting systemic extracellular matrix involvement
- Literature review of 72 genetically confirmed FNG cases identified the heparin-binding domain as a mutational hotspot
- Study demonstrates the value of fibronectin staining and FN1 genetic testing for diagnosis of atypical membranoproliferative glomerulonephritis
Limitations
This is a single case report with limited generalizability. The findings are specific to one patient's rare genetic condition and do not address broader child health or well-being outcomes relevant to low-income or middle-income settings.
Abstract
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.