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Abstract: TH-PO526

A Case of Sporadic Glomerulopathy with Fibronectin Deposits with a Mutation in FN1

Session Information

  • Trainee Case Reports - I
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Misawa, Hideo, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
  • Takeda, Tetsuro, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
  • Ueda, Yoshihiko, Saitama Medical Center, Koshigaya, Japan
Introduction

Glomerulopathy with fibronectin deposits (GFND) is a rare renal disease with massive mesangial, and subendothelial fibronectin deposits. It presents proteinuria, often in the nephrotic range in the third to fourth decade, and slow progression to end-stage renal disease. Here we describe a case with GFND from a genetic mutation.

Case Description

A 52-year-old lady presented with edema and 2-year-history of hypertension. Since 6 years ago, mild proteinuria and microscopic hematuria have been detected by regular health check-up. Family history was negative for any kidney diseases. She was diagnosed as having nephrotic syndrome (massive proteinuria, 7.7 g/gCr, hypoalbuminemia, 2.6 g/dl, normal level of creatinine of 0.42 mg/dl). A renal biopsy showed lobular appearance and membranoproliferative glomerulonephritis-like lesions on light microscopy. Electron microscopy revealed homogeneous granular fine fibers. In a case with micro-fibrillar deposits in glomeruli, it is necessary to rule out an amyloidosis and a glomerulopathy derived from immunoglobulins. In this case, Direct Fast Scarlet staining and immunofluorescence were all negative. Following the above results, we suspected her of GFND. Next, we carried out mass spectrometry to identify the origin of deposits in laser micro-dissected glomeruli. Majority of detected proteins was fibronectin. Furthermore, immunohistochemistry of the fibronectin showed intense staining in the mesangium and subendothelium. Thus, she was diagnosed as having GFND. We performed genetic analysis to identify mutations of fibronectin 1 gene (FN1) and found heterozygous deletional mutation (p.Pro1472del).

Discussion

Clinically, it has been difficult to identify the origin of glomerular deposition especially in a case with micro-fibrillar deposits. However, laser micro-dissection and mass spectrometry could accurately identify the major protein of deposits, leading to a diagnosis with GFND.
GFND is a rare inherited autosomal dominant disease and 60% of the cases have mutations in the FN1. Recently, 11 pathogenic variations (10 exonic and one intonic) in the FN1 have been reported. In exonic variants, only one is in the integrin-binding domain, the others are in the heparin-binding domain. In this case we detected deletional mutation in the integrin-binding domain (p.Pro1472del) which was consistent with those reported by others.