Glomerulopathy with Fibronectin Deposits 2 (GFND2)

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OMIM 56 601894 OMIM Phenotypic Series 56 PS137950 KEGG 36 H01260 ICD10 via Orphanet 33 N07.6 UMLS via Orphanet 72 C1866075 C3888104

Orphanet 58 ORPHA84090 MedGen 41 C1866075 SNOMED-CT via HPO 68 102572006 119247004 197679002 197940006 230706003 236423003 24184005 263681008 274100004 29738008 38341003 41607009 42399005 433146000 52254009 702391001 more UMLS 71 C0403556 C0403557 C1866075 C3888104 more

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 84090 Definition A primary glomerular disease characterized by proteinuria , type IV renal tubular acidosis, microscopic hematuria and hypertension that may lead to end-stage renal failure in the second to sixth decade of life. Epidemiology Fibronectin glomerulopathy exact prevalence is unknown. Only 20 families and 25 sporadic cases have been described in the literature so far. Clinical description Fibronectin glomerulopathy may present at different ages, although mostly in adolescence or early adulthood, with typical features of a nephrotic syndrome including hypertension, which can be severe, and edema, which initially develops around the eyes and legs but with time may become generalized. Patients may also present with varying degrees of renal failure that progressively worsen over several years, reaching end stage renal disease in the second to sixth decade of life. Etiology Clustering of the disease within families indicates a genetic origin. In 40% of families, the disease is caused by heterozygous mutations in the FN1 gene (2q34) encoding fibronectin. Whole-genome linkage analysis in a large pedigree showed another disease locus on 1q32, however no specific candidate genes has been identified so far. Diagnostic methods Diagnosis rests on renal biopsy . Typical findings at light microscopy are enlarged glomeruli with deposits in the mesangium and subendothelial space, usually with scant immunoreactivity for immunoglobulins or complement factors. Electron microscopy reveals deposits mainly located in the subendothelial space but also in the subepithelial and intramembranous spaces. Homogeneous granular deposits dominate in most cases; in some an admixture of fibrils is observed. The most striking finding is the immunoreactivity of the glomerular deposits to fibronectin. Family history is supportive of the diagnosis. Differential diagnosis Differential diagnosis includes other chronic non-amyloid glomerulopathies with organized deposits including mixed cryoglobulinemia, fibrillary glomerulonephritis, immunotactoid glomerulopathy, collagen type III glomerulopathy, systemic lupus erythematosus, diabetes glomerulopathy and other non-specific collagen deposition diseases. It is difficult to discriminate fibronectin glomerulopathy from membranoproliferative glomerulonephritis at light microscopy examination. Genetic counseling Segregation with disease appearance in successive generations is consistent with an autosomal dominant pattern of inheritance with age-related penetrance. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring. Management and treatment There is no specific treatment for fibronectin glomerulopathy. Treatment of symptoms can include corticosteroids , diuretics and treatment for hypertension. Antiproteinuric and renoprotective treatment with ACE inhibitors or anti-AT1R antagonists could be of help to slow renal disease progression. More advanced cases of renal failure require renal dialysis or transplantation. Prognosis Prognosis is uncertain, in some cases the disease follows an indolent course and in others it leads to end stage renal disease and chronic renal failure in the second to sixth decade of life. Visit the Orphanet disease page for more resources.

MalaCards based summary : Glomerulopathy with Fibronectin Deposits 2, also known as fibronectin glomerulopathy, is related to glomerulopathy with fibronectin deposits 1 and nephrotic syndrome. An important gene associated with Glomerulopathy with Fibronectin Deposits 2 is FN1 (Fibronectin 1), and among its related pathways/superpathways are Focal adhesion and ECM-receptor interaction. Affiliated tissues include kidney and eye, and related phenotypes are proteinuria and renal insufficiency

Genetics Home Reference : ²⁵ Fibronectin glomerulopathy is a kidney disease that usually develops between early and mid-adulthood but can occur at any age. It eventually leads to irreversible kidney failure (end-stage renal disease). Individuals with fibronectin glomerulopathy usually have blood and excess protein in their urine (hematuria and proteinuria, respectively). They also have high blood pressure (hypertension). Some affected individuals develop renal tubular acidosis, which occurs when the kidneys are unable to remove enough acid from the body and the blood becomes too acidic. The kidneys of people with fibronectin glomerulopathy have large deposits of the protein fibronectin-1 in structures called glomeruli. These structures are clusters of tiny blood vessels in the kidneys that filter waste products from blood. The waste products are then released in urine. The fibronectin-1 deposits impair the glomeruli's filtration ability. Fifteen to 20 years following the appearance of signs and symptoms, individuals with fibronectin glomerulopathy often develop end-stage renal disease. Affected individuals may receive treatment in the form of a kidney transplant; in some cases, fibronectin glomerulopathy comes back (recurs) following transplantation.

OMIM : ⁵⁶ Glomerulopathy with fibronectin deposits is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Pathologic examination shows enlarged glomeruli with mesangial and subendothelial fibrillary deposits that show strong immunoreactivity to fibronectin (Castelletti et al., 2008). For a discussion of genetic heterogeneity of GFND, see 137950. (601894)

KEGG : ³⁶ Glomerulopathy with fibronectin deposits (GFND) is a hereditary kidney disease with proteinuria, microscopic hematuria, and hypertension that lead to end-stage renal failure in the second to sixth decade of life. It has been reported that mutations in FN1, which encodes fibronectin, are the cause of GFND.

UniProtKB/Swiss-Prot : ⁷³ Glomerulopathy with fibronectin deposits 2: Genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life.

Clinical features from OMIM:

601894

Search Clinical Trials , NIH Clinical Center for Glomerulopathy with Fibronectin Deposits 2

Search GEO for disease gene expression data for Glomerulopathy with Fibronectin Deposits 2.