GFND2
MCID: GLM015
MIFTS: 34

Glomerulopathy with Fibronectin Deposits 2 (GFND2)

Categories: Genetic diseases, Immune diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Glomerulopathy with Fibronectin Deposits 2

MalaCards integrated aliases for Glomerulopathy with Fibronectin Deposits 2:

Name: Glomerulopathy with Fibronectin Deposits 2 56 52 73 29 13 6 71
Fibronectin Glomerulopathy 56 52 25 58 73
Glomerulopathy with Fibronectin Deposits 25 58 36 71
Gfnd2 56 52 73
Familial Glomerular Nephritis with Fibronectin Deposits 25 73
Glomerulopathy with Giant Fibrillar Deposits 25 71
Familial Lobular Glomerulopathy 25 71
Gfnd 25 58
Glomerular Nephritis, Familial, with Fibronectin Deposits 56
Glomerular Nephritis Familial with Fibronectin Deposits 52
Glomerulopathy, with Fibronectin Deposits, Type 2 39
Glomerulopathy, with Fibronectin Deposits 39

Characteristics:

Orphanet epidemiological data:

58
fibronectin glomerulopathy
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

56
Miscellaneous:
slow progression
onset of end-stage renal disease 15 to 20 years after onset
onset of proteinuria in the second to fourth decades

Inheritance:
autosomal dominant


HPO:

31
glomerulopathy with fibronectin deposits 2:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare renal diseases


External Ids:

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
UMLS 71 C0403556 C0403557 C1866075 more

Summaries for Glomerulopathy with Fibronectin Deposits 2

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.

Related Diseases for Glomerulopathy with Fibronectin Deposits 2

Graphical network of the top 20 diseases related to Glomerulopathy with Fibronectin Deposits 2:



Diseases related to Glomerulopathy with Fibronectin Deposits 2

Symptoms & Phenotypes for Glomerulopathy with Fibronectin Deposits 2

Human phenotypes related to Glomerulopathy with Fibronectin Deposits 2:

58 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 proteinuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0000093
2 renal insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0000083
3 hypertension 58 31 hallmark (90%) Very frequent (99-80%) HP:0000822
4 nephrotic syndrome 58 31 hallmark (90%) Very frequent (99-80%) HP:0000100
5 glomerulopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0100820
6 hypoalbuminemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003073
7 pedal edema 58 31 hallmark (90%) Very frequent (99-80%) HP:0010741
8 microscopic hematuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0002907
9 mesangial abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0001966
10 cerebral hemorrhage 58 31 occasional (7.5%) Occasional (29-5%) HP:0001342
11 renal cell carcinoma 31 HP:0005584
12 stage 5 chronic kidney disease 31 HP:0003774
13 generalized distal tubular acidosis 31 HP:0004916

Symptoms via clinical synopsis from OMIM:

56
Genitourinary Kidneys:
proteinuria
nephrotic syndrome
microscopic hematuria
renal failure
enlarged glomeruli
more
Cardiovascular Vascular:
hypertension due to renal disease

Clinical features from OMIM:

601894

Drugs & Therapeutics for Glomerulopathy with Fibronectin Deposits 2

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

Genetic Tests for Glomerulopathy with Fibronectin Deposits 2

Genetic tests related to Glomerulopathy with Fibronectin Deposits 2:

# Genetic test Affiliating Genes
1 Glomerulopathy with Fibronectin Deposits 2 29 FN1

Anatomical Context for Glomerulopathy with Fibronectin Deposits 2

MalaCards organs/tissues related to Glomerulopathy with Fibronectin Deposits 2:

40
Kidney, Eye

Publications for Glomerulopathy with Fibronectin Deposits 2

Articles related to Glomerulopathy with Fibronectin Deposits 2:

(show all 32)
# Title Authors PMID Year
1
Fibronectin glomerulopathy with nephrotic syndrome in a 3-year-old male. 56 6 61
12042895 2002
2
Mutations in FN1 cause glomerulopathy with fibronectin deposits. 56 6
18268355 2008
3
Glomerulopathy associated with predominant fibronectin deposits: a newly recognized hereditary disease. 56 6
7564073 1995
4
Familial glomerulonephritis characterized by massive deposits of fibronectin. 6 56
7747733 1995
5
Glomerulonephritis with organized deposits: a mesangiopathic, not immune complex-mediated disease? A pathologic study of two cases in the same family. 6 56
1544672 1992
6
Fibronectin glomerulopathy: A case report and literature review. 61
32402469 2020
7
A novel variant in FN1 in a family with fibronectin glomerulopathy. 61
30820325 2019
8
Fibronectin Glomerulopathy Caused by the Y973C Mutation in Fibronectin: A Case Report and Literature Review. 61
29620516 2018
9
Fibronectin glomerulopathy - A sporadic case with unusual clinical manifestation. 61
29265057 2017
10
AJKD Atlas of Renal Pathology: Fibronectin Glomerulopathy. 61
29055354 2017
11
Fibronectin Glomerulopathy: A Rare Autosomal Dominant Glomerular Disease. 61
28875965 2017
12
Fibronectin glomerulopathy complicated with persistent cloaca and congenital esophageal atresia: a case report and literature review. 61
28877681 2017
13
A Case of Fibronectin Glomerulopathy Caused by Missense Mutations in the Fibronectin 1 Gene. 61
29270505 2017
14
Fibronectin Conformation and Assembly: Analysis of Fibronectin Deletion Mutants and Fibronectin Glomerulopathy (GFND) Mutants. 61
28745050 2017
15
Fibronectin glomerulopathy in a 88 year-old male with acute kidney injury on chronic kidney disease: A case report and a review of the literature. 61
27836185 2017
16
Clinical and morphological features of fibronectin glomerulopathy: a report of ten patients from a single institution. 61
25601194 2015
17
Fibronectin glomerulopathy. 61
26064516 2013
18
Fibronectin glomerulopathy: an unusual cause of adult-onset nephrotic syndrome. 61
22721928 2012
19
A recurrent fibronectin glomerulopathy in a renal transplant patient: a case report. 61
22747478 2012
20
Characterization of glomerular diseases using proteomic analysis of laser capture microdissected glomeruli. 61
22282304 2012
21
Fibronectin glomerulopathy in a 34-year-old man: a case report. 61
20594046 2010
22
An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review. 61
20497759 2010
23
Fibronectin non-amyloid glomerulopathy. 61
20126589 2009
24
Fibronectin glomerulopathy: an uncommon cause of nephrotic syndrome in systemic lupus erythematosus. 61
25983887 2008
25
[Fibronectin glomerulopathy: report of a case]. 61
17374244 2007
26
Glomerulopathies with organized deposits. 61
12180633 2002
27
[Clinicopathological and morphometrical analysis of 5 cases from 4 families of fibronectin glomerulopathy]. 61
10361419 1999
28
The gene for human fibronectin glomerulopathy maps to 1q32, in the region of the regulation of complement activation gene cluster. 61
9837825 1998
29
Exclusion of the uteroglobin gene as a candidate for fibronectin glomerulopathy (GFND) 61
9761542 1998
30
Glomerular pathology: recent advances. 61
9602701 1998
31
[Fibrillary glomerulonephritis. Case report for differential nephrotic syndrome diagnosis]. 61
9556799 1998
32
Newer glomerular diseases. 61
9125794 1996

Variations for Glomerulopathy with Fibronectin Deposits 2

ClinVar genetic disease variations for Glomerulopathy with Fibronectin Deposits 2:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FN1 NM_002026.3(FN1):c.5500T>A (p.Trp1834Arg)SNV Pathogenic 16323 rs137854486 2:216241335-216241335 2:215376612-215376612
2 FN1 NM_002026.3(FN1):c.5648T>G (p.Leu1883Arg)SNV Pathogenic 16324 rs137854487 2:216240408-216240408 2:215375685-215375685
3 FN1 NM_002026.3(FN1):c.2918A>G (p.Tyr973Cys)SNV Pathogenic 16325 rs137854488 2:216271029-216271029 2:215406306-215406306
4 FN1 NM_212482.3(FN1):c.5775G>C (p.Trp1925Cys)SNV Pathogenic 192244 rs869025198 2:216241333-216241333 2:215376610-215376610
5 FN1 NM_002026.3(FN1):c.4139_4141CTC[1] (p.Pro1381del)short repeat Pathogenic 192246 rs869025199 2:216251607-216251609 2:215386884-215386886
6 FN1 NM_212482.3(FN1):c.5921T>C (p.Leu1974Pro)SNV Pathogenic 192245 rs137854487 2:216240408-216240408 2:215375685-215375685
7 FN1 NM_212482.3(FN1):c.1757A>G (p.Gln586Arg)SNV Uncertain significance 816643 rs138219703 2:216284027-216284027 2:215419304-215419304
8 FN1 NM_002026.3(FN1):c.6410_6412ACA[1] (p.Asn2138del)deletion Uncertain significance 830028 2:216235089-216235091 2:215370366-215370368
9 FN1 NM_212482.3(FN1):c.5651A>G (p.Tyr1884Cys)SNV not provided 585091 rs199890235 2:216242957-216242957 2:215378234-215378234

UniProtKB/Swiss-Prot genetic disease variations for Glomerulopathy with Fibronectin Deposits 2:

73
# Symbol AA change Variation ID SNP ID
1 FN1 p.Tyr973Cys VAR_043918 rs137854488
2 FN1 p.Trp1925Arg VAR_043919 rs137854486
3 FN1 p.Leu1974Arg VAR_043920 rs137854487

Expression for Glomerulopathy with Fibronectin Deposits 2

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

Pathways for Glomerulopathy with Fibronectin Deposits 2

Pathways related to Glomerulopathy with Fibronectin Deposits 2 according to KEGG:

36
# Name Kegg Source Accession
1 Focal adhesion hsa04510
2 ECM-receptor interaction hsa04512
3 Regulation of actin cytoskeleton hsa04810

GO Terms for Glomerulopathy with Fibronectin Deposits 2

Sources for Glomerulopathy with Fibronectin Deposits 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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28 GO
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30 HMDB
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32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
37 LifeMap
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43 MeSH
44 MESH via Orphanet
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53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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