Glomerulopathy associated with predominant fibronectin deposits: A newly recognized hereditary disease

Abstract

A newly recognized type of familial glomerulopathy observed in patients of both sexes in six families is reported. Proteinuria, often within the nephrotic range, microscopic hematuria, hypertension and a slowly decreasing renal function over several years were common. No underlying systemic diseases were identified. Generally, light microscopy showed enlarged glomeruli with minimal hypercellularity and with extensive deposits in the mesangium and subendothelial space. By electron microscopy, granular deposits with some admixture of fibrils were most common. In one family, the deposits were predominantly fibrillary. Immunoglobulins and complement factors were inconstant or lacking. A main finding was a strong immune reactivity to fibronectin, corresponding to the distribution of the deposits. In one patient, the deposits recurred in a renal transplant. There was no indication of systemic deposition. Abnormalities in the metabolism of circulating fibronectin may play a pathogenetic role in this disease of probably autosomal dominant inheritance.

Mutations in FN1 cause glomerulopathy with fibronectin deposits

“…FN was mainly stained by an antibody detecting both plasma and cell-derived FN and to much lesser degree by an antibody specific for only cell-FN (8), suggesting that the FN that accumulated in the glomeruli was mainly derived from the plasma (9). By electron microscopy, the deposits were mainly granular (1,8).…”

“…This is an Italian family that has been partially described (1) and was updated in the present paper. Overall, eight subjects in this pedigree [three previously described (1) and five newly reported in this paper] were affected by the disease in accordance with the criteria described in Methods. Five of them underwent renal biopsy showing enlarged glomeruli with extensive deposits in the mesangium and subendothelial space that stained very strongly for FN.…”

“…The condition was recognized as a distinct disease entity by Strom et al (1). Light microscopy demonstrated enlarged glomeruli with deposits in the mesangium and subendothelial space, with scant immunoreactivity for immunoglobulins or complement factors (1). The most striking finding in this disease is strong immune reactivity of the glomerular deposits to FN (1), an adhesive high-molecular-weight dimeric glycoprotein that is part of extracellular matrix (2).…”

“…The condition was recognized as a distinct disease entity by Strom et al (1). Light microscopy demonstrated enlarged glomeruli with deposits in the mesangium and subendothelial space, with scant immunoreactivity for immunoglobulins or complement factors (1).…”

Glomerulopathy with distinctive fibrillar deposits but lacking glomerular deposition of type III collagen

“…Among those with non-amyloid origins, the deposits which are composed of immunoglobulin components are seen in fibrillary glomerulonephritis, immunotactoid glomerulopathy, cryoglobulinemic glomerulonephritis, and light and/or heavy chain-deposition disease; those without immunoglobulin components are seen in fibronectin glomerulopathy, nail-patella syndrome, collagenofibrotic glomerulopathy, fibrin tactoids in inflammatory glomerular diseases, and diabetic nephropathy [1,2]. The electron-dense deposits in fibronectin glomerulopathy, an autosomal dominant hereditary disorder characterized by large mesangial and subendothelial electron-dense deposits composed of fibronectin, are predominantly amorphous and granular, but they may contain electron-lucent areas and scattered, focal fine filaments 10-14 nm in diameter [3,4].…”