MCID: GLM015
MIFTS: 30

Glomerulopathy with Fibronectin Deposits 2

Categories: Genetic diseases, Rare diseases, Nephrological diseases

Aliases & Classifications for Glomerulopathy with Fibronectin Deposits 2

MalaCards integrated aliases for Glomerulopathy with Fibronectin Deposits 2:

Name: Glomerulopathy with Fibronectin Deposits 2 53 49 71 28 13 69
Fibronectin Glomerulopathy 53 49 24 55 71
Glomerulopathy with Fibronectin Deposits 24 55 36 69
Gfnd2 53 49 71
Familial Glomerular Nephritis with Fibronectin Deposits 24 71
Glomerulopathy with Giant Fibrillar Deposits 24 69
Familial Lobular Glomerulopathy 24 69
Gfnd 24 55
Glomerular Nephritis, Familial, with Fibronectin Deposits 53
Glomerular Nephritis Familial with Fibronectin Deposits 49

Characteristics:

Orphanet epidemiological data:

55
fibronectin glomerulopathy
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

53
Inheritance:
autosomal dominant

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


HPO:

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


Classifications:

Orphanet: 55  
Rare renal diseases


External Ids:

OMIM 53 601894
Orphanet 55 ORPHA84090
UMLS via Orphanet 70 C3888104 C1866075
ICD10 via Orphanet 33 N07.6
MedGen 39 C1866075
KEGG 36 H01260

Summaries for Glomerulopathy with Fibronectin Deposits 2

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 84090Disease definitionFibronectin glomerulopathy is a hereditary kidney 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.EpidemiologyIt is a very rare disease. The exact prevalence is unknown. Only 16 families have been described in the literature so far.Clinical descriptionFibronectin 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. Biochemical analysis shows microscopic hematuria and proteinuria with hypoalbuminemia. 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.EtiologyClustering of the disease within families indicates a genetic origin, and segregation with disease appearance in successive generations is consistent with an autosomal dominant pattern of inheritance with age-related penetrance. In 40% of families the disease is caused by heterozygousmutations in the FN1 gene (2q34) encoding fibronectin. However, genetic heterogeneity is suspected. Whole-genomelinkage analysis in a large pedigree showed another disease locus on 1q32, however no specific candidate genes has been identified so far.Diagnostic methodsDiagnosis rests on renal biopsy. Typical findings at light microscopy are enlarged glomeruli with deposits in the mesangium and subendothelial space, 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 diagnosisDifferential diagnosis includes other chronic non-amyloid glomerulopathies with organized deposits including mixed cryoglobulinemia, fibrillary glomerulonephritis, immunotactoid glomerulopathy, collagen type III glomerulopathy, systemic lupus erythematosus (see these terms), diabetes glomerulopathy and other non-specific collagen deposition diseases. It is difficult to discriminate fibronectin glomerulopathy from membranoproliferative glomerulonephritis (see this term) at light microscopy examination. In all cases strong immunohistochemical positivity to fibronectin is mandatory for differential diagnosis.Genetic counselingGenetic counseling is useful for children of affected subjects with FN1 mutations to identify carriers that are at risk of developing the disease later in life. Monitoring these subjects for proteinuria could allow early treatment with angiotensin inhibitors to delay onset of renal dysfunction.Management and treatmentThere 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.PrognosisPrognosis 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. Last updated: 5/10/2010

MalaCards based summary : Glomerulopathy with Fibronectin Deposits 2, also known as fibronectin glomerulopathy, is related to glomerulopathy with fibronectin deposits 1 and tracheoesophageal fistula with or without esophageal atresia, and has symptoms including hypertension, renal insufficiency and proteinuria. 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.

OMIM : 53 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)

UniProtKB/Swiss-Prot : 71 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.

Genetics Home Reference : 24 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).

Related Diseases for Glomerulopathy with Fibronectin Deposits 2

Diseases in the Glomerulopathy with Fibronectin Deposits 2 family:

Glomerulopathy with Fibronectin Deposits 1

Diseases related to Glomerulopathy with Fibronectin Deposits 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 glomerulopathy with fibronectin deposits 1 10.9
2 tracheoesophageal fistula with or without esophageal atresia 9.8
3 esophageal atresia 9.8
4 nephrotic syndrome 9.8
5 esophagitis 9.8

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

Symptoms via clinical synopsis from OMIM:

53
Genitourinary Kidneys:
proteinuria
nephrotic syndrome
microscopic hematuria
renal failure
enlarged glomeruli
more
Cardiovascular Vascular:
hypertension due to renal disease


Clinical features from OMIM:

601894

Human phenotypes related to Glomerulopathy with Fibronectin Deposits 2:

55 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertension 55 31 hallmark (90%) Very frequent (99-80%) HP:0000822
2 renal insufficiency 55 31 hallmark (90%) Very frequent (99-80%) HP:0000083
3 proteinuria 55 31 hallmark (90%) Very frequent (99-80%) HP:0000093
4 nephrotic syndrome 55 31 hallmark (90%) Very frequent (99-80%) HP:0000100
5 glomerulopathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0100820
6 cerebral hemorrhage 55 31 occasional (7.5%) Occasional (29-5%) HP:0001342
7 edema of the lower limbs 55 31 hallmark (90%) Very frequent (99-80%) HP:0010741
8 hypoalbuminemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0003073
9 microscopic hematuria 55 31 hallmark (90%) Very frequent (99-80%) HP:0002907
10 mesangial abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0001966
11 renal cell carcinoma 31 HP:0005584
12 stage 5 chronic kidney disease 31 HP:0003774
13 generalized distal tubular acidosis 31 HP:0004916

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 28 FN1

Anatomical Context for Glomerulopathy with Fibronectin Deposits 2

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

38
Kidney, Eye

Publications for Glomerulopathy with Fibronectin Deposits 2

Articles related to Glomerulopathy with Fibronectin Deposits 2:

# Title Authors Year
1
Fibronectin glomerulopathy complicated with persistent cloaca and congenital esophageal atresia: a case report and literature review. ( 28877681 )
2017
2
Fibronectin Conformation and Assembly: Analysis of Fibronectin Deletion Mutants and Fibronectin Glomerulopathy (GFND) Mutants. ( 28745050 )
2017
3
Fibronectin glomerulopathy: an unusual cause of adult-onset nephrotic syndrome. ( 22721928 )
2012
4
The gene for human fibronectin glomerulopathy maps to 1q32, in the region of the regulation of complement activation gene cluster. ( 9837825 )
1998

Variations for Glomerulopathy with Fibronectin Deposits 2

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

71
# Symbol AA change Variation ID SNP ID
1 FN1 p.Tyr973Cys VAR_043918 rs137854488
2 FN1 p.Trp1834Arg VAR_043919 rs137854486
3 FN1 p.Leu1883Arg VAR_043920 rs137854487

ClinVar genetic disease variations for Glomerulopathy with Fibronectin Deposits 2:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 FN1 NM_212482.2(FN1): c.5773T> A (p.Trp1925Arg) single nucleotide variant Pathogenic rs137854486 GRCh37 Chromosome 2, 216241335: 216241335
2 FN1 NM_212482.2(FN1): c.5921T> G (p.Leu1974Arg) single nucleotide variant Pathogenic rs137854487 GRCh37 Chromosome 2, 216240408: 216240408
3 FN1 NM_212482.2(FN1): c.2918A> G (p.Tyr973Cys) single nucleotide variant Pathogenic rs137854488 GRCh37 Chromosome 2, 216271029: 216271029
4 FN1 NM_212482.2(FN1): c.5921T> C (p.Leu1974Pro) single nucleotide variant Pathogenic rs137854487 GRCh37 Chromosome 2, 216240408: 216240408
5 FN1 NM_212482.2(FN1): c.5775G> C (p.Trp1925Cys) single nucleotide variant Pathogenic rs869025198 GRCh37 Chromosome 2, 216241333: 216241333
6 FN1 NM_212482.2(FN1): c.4414_4416delCCT (p.Pro1472del) deletion Pathogenic rs869025199 GRCh37 Chromosome 2, 216251608: 216251610

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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
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45 NCI
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50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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