Collagenofibrotic Glomerulopathy: Three Case Reports in Brazil

<p>Abstract</p> <p>Background</p> <p>We are reporting the first Collagenofibrotic Glomerulopathy (CG) in South America. So, this collagen type III glomerulopathy is not limited to Japan but may be found throughout the world.</p> <p>Case Reports</p> <p>We describe three patients that presented some factors in common, such as sex, age and the presence of non-nephrotic proteinuria associated with microscopic hematuria. The findings with the immunofluorescence microscopy, of immunoglobulins, and components of the complement were usually negative. The picrosyrius staining showed the presence of reddish material in the mesangium, when it was seen under standard microscopy; however, when it was seen with birefringence, it became greenish under polarized light, showed the collagen found in this area of the glomerulus. The identification of CG was made through electronic microscopic scanning, and curved and disorganized fibers were found.</p> <p>Conclusion</p> <p>These cases are the first from South America to be reported, and they are about an idiopathic renal disease that is not related to any specific races or locations. The reports contribute to a better understanding of this disease, which although not so prevalent, should be considered as an importantly differential diagnostic of cases of proteinuria.</p

A novel single amino acid deletion impairs fibronectin function and causes familial glomerulopathy with fibronectin deposits: case report of a family

Abstract Background Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin. Case presentation This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality. Conclusion The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.https://deepblue.lib.umich.edu/bitstream/2027.42/152212/1/12882_2019_Article_1507.pd