Clinical Observation Of Three Fibronectin Nephropathy Pedigrees And Pathogenicity Analysis Of FN1 Gene Mutation

Background and Objectives:Glomerulopathy with fibronectin deposits?GFND?is a rare kidney disease.The common clinical manifestations of GFND are proteinuria,hematuria,hypertension and an indolent course of renal function deterioration.Due to its non-specific clinical manifestations,the diagnosis of GFND is mainly based on renal pathology.In general,there appears mesangial nodular glomerulopathy in light microscopy.A strong stain with monoclonal antibody for fibronectin is displayed in the deposits in the expend mesangium and endothelium during the immunohistochemistry staining.Electron microscopy showed that fibers with a diameter of 12-16 nm deposited in the mesangial area and under the endothelium.The incidence of GFND shows no gender preference and it often is not sporadic,therefore it is considered to be an autosomal dominant genetic disease.The mutation of FN1 gene located in 2q35 has been found to be closely related to its onset.However,not all individuals carryring the FN1 mutants bear the disease.On the other hand,patients with fibronectin nephropathy detect no FN1 mutation occasionally.Therefore,in order to further figure out the influence of FN1 gene mutation and its onset in patients with fibronectin nephropathy,explore the pathogenesis,explore the treatment and evaluate the prognosis,we conducted this study.Methods:The clinical manifestations and biochemical characteristics of four patients who were admitted to Department of Nephropathy of the First Affiliated Hospital of Zhengzhou University form January 2012 to June 2017 were collected.All the patients was diagnosed by renal biopsy.The consent forms of patients and their families were obtained.Laboratory tests including renal function,urine routine,24-hour urinary total protein were carried out.FN1 gene were detected as well.Result:1.A total of three mutation sites were identified for the FN1 gene,namely c.4374₄376del,c.5773T>C,and c.2918A>G.The c.4374₄376del mutation resulted in the deletion of temination codon at 1459 sites.The c.5773T>C mutation resulted in the exchanging of amino acid at 1925 site from tryptophan to arginine,and the c.2918A>G mutation resulted in the exchanging of amino acid at 973 site from tyrosine to cysteine.2.FN1 mutations were detected in seven individuals from three families,five of whom were ill,and the left two was a 14-year-old mutant male and 2-year-old female,these two persons are mutation gene carriers.3.The clinical manifestations of patients were proteinuria,hypertension,and an indolent course of renal function deterioration,however without hematuria.4.RAAS inhibitors can help to reduce urinary protein,but can not prevent the deterioration of renal function.Glucocorticoid combined with cyclosporine may help to reduce urinary protein in the short term.Conclusions:In this study,three mutation sites were found,of which one was a new mutation site locating in the integrin-binding domain?c.4374₄376del?,and one new mutation located in ? 13 heparin-binding domain namely c.5773T>C.These new mutations enriched the human gene mutation library,providing new ideas for further studies and differential diagnosis.Fibronectin nephropathy is not a immune-related disease,so there is no specific treatment for this disease.However,in our study,by applying glucocorticoid combined with cyclosporine to the patients,urinary protein was significantly reduced in a short period of time.However,whether this treatment is helpful for the patients remains unknown.Longer time and more cases may help to draw the conclusion.