A new complement factor B mutation associated with crescentic C3 glomerulopathy; a case report

Abstract

Background: C3 glomerulopathy is a recently described entity classified as complementassociated glomerular disease. Case Presentation: We report a case of a 48-year-old man referred to the nephrology department for nephrotic syndrome with rapidly progressive kidney failure, acquired partial lipodystrophy and drusen in Bruch’s membrane of the retina. Blood tests showed low C3 and no evidence for autoimmune diseases, monoclonal gammopathy or infection. The renal biopsy revealed a proliferative endocapillary and crescentic glomerulonephritis with glomerular deposits exclusively of C3 and significant interstitial fibrosis. The electronic microscopy was consistent with dense deposit disease. The complement analysis revealed a pathogenic mutation of the complement factor B (CFB) gene not previously described in literature. Conclusions: The authors report a new mutation of CFB, in a dense deposit disease patient; this finding brings a new insight to the pathogenic pathway of C3 glomerulopathy and possibly to other complement dysregulation associated glomerular diseases. More clinical trials are needed to clarify both the pathogenicity and the optimal treatment for these entities.

Adjustment of p-Value Expression To Ontology Using Machine Learning For Genetic Prediction, Prioritization, Interaction, And Its Validation In Glomerular Disease

“…The term C3 glomerulopathy (C3G) is a group of related conditions that cause the malfunction of the kidneys [1], characterized by the presence of glomerular deposits composed of C3 [2]. These glomerular diseases (GD) include many conditions with a variety of genetic/environmental causes [3].C3G is associated with changes (mutation) in many genes. Most of these genes provide instructions for making proteins that help to regulate a part of the body's immune response known as the complement system [4].…”

“…This system works together as a group of proteins to destroy foreign invaders/trigger/inflammation. A specific mutation in the complement system-related genes, like C3, ADAM19, ADAMTS13, C3AR1, C8A, CD46, CFB, CFD, CFI, CFHR (1)(2)(3)(4)(5) and as well as other complement system-related genes [5,6], risk haplotypes of CFH and CD46 have been identified that modify disease penetration and severity [7,8]. In most cases, the cause of the C3G is unknown.…”