MCID: DNY001
MIFTS: 53

Denys-Drash Syndrome malady

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Reproductive diseases, Endocrine diseases, Fetal diseases

Aliases & Classifications for Denys-Drash Syndrome

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Sources:
50OMIM, 33LifeMap Discovery®, 11Disease Ontology, 46NIH Rare Diseases, 23GeneTests, 24Genetics Home Reference, 13DISEASES, 52Orphanet, 68UniProtKB/Swiss-Prot, 12diseasecard, 48Novoseek, 37MeSH, 66UMLS, 25GTR, 43NCIt, 29ICD10 via Orphanet, 38MESH via Orphanet, 67UMLS via Orphanet, 35MedGen, 60SNOMED-CT, 62The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Denys-Drash Syndrome:

Name: Denys-Drash Syndrome 50 33 11 46 23 24 13 52 68 12 48 37 66
Drash Syndrome 46 23 24 52 25
Wilms Tumor and Pseudohermaphroditism 46 23 24 52
Nephropathy, Wilms Tumor, and Genital Anomalies 46 24
 
Dds 24 68
Nephropathy Associated with Male Pseudohermaphroditism and Wilms' Tumor 46
Pseudohermaphroditism, Nephron Disorder and Wilms' Tumor 46

Characteristics:

Orphanet epidemiological data:

52
denys-drash syndrome:
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

62
denys-drash syndrome:
Inheritance: autosomal dominant inheritance, somatic mutation


Classifications:



External Ids:

OMIM50 194080
Disease Ontology11 DOID:3764
MeSH37 D030321
NCIt43 C84668
Orphanet52 ORPHA220
SNOMED-CT60 236385009
ICD10 via Orphanet29 N04.1
MESH via Orphanet38 D030321
UMLS via Orphanet67 C0950121
MedGen35 C0950121

Summaries for Denys-Drash Syndrome

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NIH Rare Diseases:46 Denys-drash syndrome is a condition that affects the kidneys and genitalia. kidney disease typically begins in the first few months of life, often leading to kidney failure in childhood. in addition, up to 90 percent of people with this condition develop a rare form of kidney cancer known as wilms tumor. males with denys-drash syndrome have gonadal dysgenesis, a condition in which the external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear to be completely female. the testes are also undescended, meaning that they remain in the pelvis, abdomen, or groin. affected females usually have normal genitalia. for this reason, females with this condition may be diagnosed with isolated nephrotic syndrome. denys-drash syndrome is caused by mutations in the wt1 gene. this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. however, most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. last updated: 10/28/2013

MalaCards based summary: Denys-Drash Syndrome, also known as drash syndrome, is related to mixed gonadal dysgenesis and dentin dysplasia, type ii, and has symptoms including male pseudohermaphroditism, proteinuria and nephrotic syndrome. An important gene associated with Denys-Drash Syndrome is WT1 (Wilms Tumor 1), and among its related pathways are Nephrin interactions and Neural Stem Cell Differentiation Pathways and Lineage-specific Markers. Affiliated tissues include kidney and testes, and related mouse phenotypes are reproductive system and endocrine/exocrine gland.

Disease Ontology:11 An autosomal dominant disease that is characterized by the association of diffuse mesangial sclerosis (dms), male pseudohermaphroditism with a 46,xy karyotype, and nephroblastoma that derives from an abnormality in the wt1 gene (wilms' tumor suppressor gene).

Genetics Home Reference:24 Denys-Drash syndrome is a condition that affects the kidneys and genitalia.

UniProtKB/Swiss-Prot:68 Denys-Drash syndrome: Typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic.

Wikipedia:69 Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or syndrome characterized by gonadal... more...

Description from OMIM:50 194080

Related Diseases for Denys-Drash Syndrome

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Diseases related to Denys-Drash Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 75)
idRelated DiseaseScoreTop Affiliating Genes
1mixed gonadal dysgenesis30.2NR5A1, WT1
2dentin dysplasia, type ii11.0
3diastrophic dysplasia11.0
4dentin dysplasia, type i, with microdontia and misshapen teeth11.0
5mohr-tranebjaerg syndrome11.0
6darier disease10.9
7dentin dysplasia10.9
8liver sarcoma10.4PAX2, WT1
9nephrotic syndrome10.4
10gonadal dysgenesis10.4
11keratosis follicularis, dwarfism, and cerebral atrophy10.4PAX2, WT1
12sclerosing hemangioma10.3PAX2, WT1
13frasier syndrome10.3
14mucinous adenofibroma10.3PAX2, WT1
15pfeiffer syndrome type 310.3NPHS1, WT1
16gonadoblastoma10.3
17glomerulosclerosis10.3
18diffuse mesangial sclerosis10.3
19testicular gonadoblastoma10.2NR5A1, WT1
20acute myeloid leukemia with cebpa somatic mutations10.2CD2AP, NPHS1
21pseudohermaphroditism10.2
22familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation10.2CD2AP, NPHS2
23lymphoma10.1
24hemolytic-uremic syndrome10.1
25pyloric stenosis10.1
26congenital diaphragmatic hernia10.1
27kidney disease10.1
28septate vagina10.1
29klinefelter's syndrome10.1NR5A1, WT1
30coronary artery disease10.1
31artery disease10.1
32endotheliitis10.1
33pfeiffer syndrome type 210.0NPHS1, NPHS2
34unna-thost palmoplantar keratoderma10.0PAX2, PDGFA, WT1
35stomatitis10.0NPHS1, NPHS2
36tooth disease10.0NR5A1, WT1
37myocardial infarction10.0
38spastic monoplegia10.0NPHS1, NPHS2
39dissociative disorder10.0
40leprosy9.9
41hypopigmentation of eyelid9.9NPHS1, NPHS2
42gastrointestinal system cancer9.8BAX, WT1
43obesity9.8
44acute myocardial infarction9.8
45end stage renal failure9.8
46gastric cancer9.8
47lepromatous leprosy9.8
48heart disease9.8
49muscular dystrophy-dystroglycanopathy , type a, 19.8CD2AP, NPHS2, PAX2
50corneal dystrophy, fuchs endothelial, 89.8NPHS1, NPHS2

Graphical network of the top 20 diseases related to Denys-Drash Syndrome:



Diseases related to denys-drash syndrome

Symptoms for Denys-Drash Syndrome

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Symptoms by clinical synopsis from OMIM:

194080

Clinical features from OMIM:

194080

HPO human phenotypes related to Denys-Drash Syndrome:

(show all 22)
id Description Frequency HPO Source Accession
1 male pseudohermaphroditism hallmark (90%) HP:0000037
2 proteinuria hallmark (90%) HP:0000093
3 nephrotic syndrome hallmark (90%) HP:0000100
4 nephropathy hallmark (90%) HP:0000112
5 nephroblastoma hallmark (90%) HP:0002667
6 hypertension typical (50%) HP:0000822
7 gonadal dysgenesis occasional (7.5%) HP:0000133
8 ambiguous genitalia, male HP:0000033
9 male pseudohermaphroditism HP:0000037
10 ambiguous genitalia, female HP:0000061
11 focal segmental glomerulosclerosis HP:0000097
12 nephrotic syndrome HP:0000100
13 nephropathy HP:0000112
14 gonadal dysgenesis HP:0000133
15 ovarian gonadoblastoma HP:0000149
16 congenital diaphragmatic hernia HP:0000776
17 hypertension HP:0000822
18 diffuse mesangial sclerosis HP:0001967
19 nephroblastoma HP:0002667
20 gonadal tissue inappropriate for external genitalia or chromosomal sex HP:0003248
21 stage 5 chronic kidney disease HP:0003774
22 true hermaphroditism HP:0010459

Drugs & Therapeutics for Denys-Drash Syndrome

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Interventional clinical trials:

idNameStatusNCT IDPhase
1Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated DiseasesCompletedNCT01252901
2Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at SanfordRecruitingNCT01793168

Search NIH Clinical Center for Denys-Drash Syndrome


Cochrane evidence based reviews: denys-drash syndrome

Genetic Tests for Denys-Drash Syndrome

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Genetic tests related to Denys-Drash Syndrome:

id Genetic test Affiliating Genes
1 Drash Syndrome25
2 Denys-Drash Syndrome23 WT1

Anatomical Context for Denys-Drash Syndrome

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MalaCards organs/tissues related to Denys-Drash Syndrome:

34
Kidney, Testes

LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Denys-Drash Syndrome:
id TissueAnatomical CompartmentCell Relevance
1 KidneyMetanephric MesenchymeMetanephric Mesenchyme Cells Affected by disease

Animal Models for Denys-Drash Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Denys-Drash Syndrome:

39
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053898.1BAX, NR5A1, PAX2, PDGFA, WT1
2MP:00053798.0BAX, CD2AP, NR5A1, PAX2, WT1
3MP:00053857.3CD2AP, NPHS2, NR5A1, PAX2, PDGFA, WT1
4MP:00053766.8BAX, CD2AP, NPHS1, NPHS2, NR5A1, PDGFA
5MP:00053676.7BAX, CD2AP, NPHS1, NPHS2, PAX2, PDGFA
6MP:00107686.5BAX, CD2AP, NPHS1, NPHS2, NR5A1, PAX2

Publications for Denys-Drash Syndrome

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Articles related to Denys-Drash Syndrome:

(show top 50)    (show all 81)
idTitleAuthorsYear
1
Bilateral Wilms' tumors in an infant with Denys-Drash syndrome and rarely seen truncation mutation in the WT1 gene-exon 6. (26628814)
2015
2
Clinical features and an atypical WT1 mutant site in a child with incomplete Denys-Drash syndrome. (24625882)
2014
3
An unusual presentation of denys-drash syndrome due to bigenic disease. (24379226)
2014
4
Denys-Drash syndrome, septated vagina and low level of anti-Mullerian hormone in male neonate. (25077094)
2014
5
A novel WT1 gene mutation in a newborn infant diagnosed with Denys-Drash syndrome. (22876585)
2012
6
A novel WT1 heterozygous nonsense mutation (p.K248X) causing a mild and slightly progressive nephropathy in a 46,XY patient with Denys-Drash syndrome. (21559934)
2011
7
Clinical pictures and novel mutations of WT1-associated Denys-Drash syndrome in two Chinese children. (21851196)
2011
8
Denys-Drash syndrome and gonadoblastoma in a patient with Klinefelter syndrome. (21552011)
2011
9
Denys-Drash syndrome with neonatal renal failure in monozygotic twins due to c.1097G&gt;A mutation in the WT1 gene. (21434831)
2011
10
A murine model of Denys-Drash syndrome reveals novel transcriptional targets of WT1 in podocytes. (19797313)
2010
11
The novel WT1 gene mutation p.H377N associated to Denys-Drash syndrome. (20562648)
2010
12
Case report: WT1 exon 6 truncation mutation and ambiguous genitalia in a patient with Denys-Drash syndrome. (18197048)
2008
13
Mixed gonadal dysgenesis and Denys-Drash syndrome: urologists should screen for nephrotic syndrome. (18163932)
2007
14
Case report: Denys- Drash syndrome. (18076855)
2007
15
A proteomic investigation of glomerular podocytes from a Denys-Drash syndrome patient with a mutation in the Wilms tumour suppressor gene WT1. (17295355)
2007
16
Denys-Drash syndrome (DDS). (16823575)
2006
17
Hydrothorax in a patient with Denys-Drash syndrome associated with a diaphragmatic defect. (16932893)
2006
18
A novel WT1 missense mutation presenting with Denys-Drash syndrome and cortical atrophy. (16303781)
2006
19
Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study. (15910385)
2005
20
Denys-Drash syndrome. (15758579)
2005
21
Denys-Drash syndrome. (15026863)
2004
22
Murine Denys-Drash syndrome: evidence of podocyte de-differentiation and systemic mediation of glomerulosclerosis. (12915483)
2003
23
A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7. (12161615)
2002
24
Wilms tumor in a pediatric renal transplant recipient with unexpected Denys-Drash syndrome. (12493420)
2002
25
Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome. (11519891)
2001
26
Novel WT1 exon 9 mutation (D396Y) in a patient with early onset Denys Drash syndrome. (10738002)
2000
27
Hemolytic uremic syndrome associated with Denys-Drash syndrome. (11045393)
2000
28
A novel missense mutation of the WT1 gene causing Denys-Drash syndrome with exceptionally mild renal manifestations. (10799199)
2000
29
Genetic analysis of two female patients with incomplete Denys-Drash syndrome. (11228042)
2000
30
WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis. (9916932)
1999
31
Transcriptional regulation of PDGF-A and TGF-beta by +KTS WT1 deletion mutants and a mutant mimicking Denys-Drash syndrome. (10586431)
1999
32
A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome. (10077614)
1999
33
In utero nephropathy, Denys-Drash syndrome and Potter phenotype. (9745866)
1998
34
Regulation of renal EGF receptor expression is normal in Denys-Drash syndrome. (9291179)
1997
35
Atypical presentation of Denys-Drash syndrome in a female with a novel Wt1 gene mutation. (9125334)
1996
36
A newly identified exonic mutation of the WT1 gene in a patient with Denys-Drash syndrome. (8741319)
1996
37
Diaphragmatic hernia in Denys-Drash syndrome. (7645607)
1995
38
Denys-Drash syndrome. (8772891)
1995
39
DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations. (7795587)
1995
40
Nephropathy with Wilms tumour or gonadal dysgenesis: incomplete Denys-Drash syndrome or separate diseases? (7556327)
1995
41
WT1 mutations associated with incomplete Denys-Drash syndrome define a domain predicted to behave in a dominant-negative fashion. (7959750)
1994
42
Further evidence that imbalance of WT1 isoforms may be involved in Denys-Drash syndrome. (8281163)
1993
43
A novel mutation of the WT1 gene (a tumor suppressor gene for Wilms' tumor) in a patient with Denys-Drash syndrome. (8281164)
1993
44
A point mutation found in the WT1 gene in a sporadic Wilms' tumor without genitourinary abnormalities is identical with the most frequent point mutation in Denys-Drash syndrome. (8381368)
1993
45
Denys-Drash syndrome: relating a clinical disorder to genetic alterations in the tumor suppressor gene WT1. (8229473)
1993
46
A novel zinc finger mutation in a patient with Denys-Drash syndrome. (8111391)
1993
47
Dominant negative mutations in the Wilms tumour (WT1) gene cause Denys-Drash syndrome--proof that a tumour-suppressor gene plays a crucial role in normal genitourinary development. (1338905)
1992
48
Inherited WT1 mutation in Denys-Drash syndrome. (1327525)
1992
49
Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome. (1338906)
1992
50
Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. (1655284)
1991

Variations for Denys-Drash Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Denys-Drash Syndrome:

68 (show all 24)
id Symbol AA change Variation ID SNP ID
1WT1p.Cys330TyrVAR_007743
2WT1p.Cys360GlyVAR_007744
3WT1p.Arg366CysVAR_007745
4WT1p.Arg366HisVAR_007746
5WT1p.His373GlnVAR_007747
6WT1p.Arg394TrpVAR_007750
7WT1p.Asp396AsnVAR_007751
8WT1p.Asp396GlyVAR_007752
9WT1p.Met342ArgVAR_015054
10WT1p.Cys355TyrVAR_015055
11WT1p.His373TyrVAR_015056
12WT1p.His377ArgVAR_015057
13WT1p.Cys385ArgVAR_015058
14WT1p.Cys388PheVAR_015059
15WT1p.Arg394GlnVAR_015061
16WT1p.Leu398ProVAR_015062
17WT1p.Cys360TyrVAR_043800
18WT1p.Arg366LeuVAR_043802
19WT1p.Gln369ProVAR_043803
20WT1p.Cys388TyrVAR_043806
21WT1p.Arg394ProVAR_043808
22WT1p.Asp396TyrVAR_043809
23WT1p.His401TyrVAR_043811
24WT1p.His405ArgVAR_043812

Clinvar genetic disease variations for Denys-Drash Syndrome:

5 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1WT1NM_024426.4(WT1): c.1384C> T (p.Arg462Trp)single nucleotide variantPathogenicrs121907900GRCh37Chr 11, 32413566: 32413566
2WT1NM_024426.4(WT1): c.1301G> A (p.Arg434His)single nucleotide variantPathogenicrs121907901GRCh37Chr 11, 32414250: 32414250
3WT1NM_024426.4(WT1): c.1391A> G (p.Asp464Gly)single nucleotide variantPathogenicrs121907902GRCh37Chr 11, 32413559: 32413559
4WT1NM_024426.4(WT1): c.1390G> A (p.Asp464Asn)single nucleotide variantPathogenicrs28941778GRCh37Chr 11, 32413560: 32413560
5WT1NM_024426.4(WT1): c.1385G> C (p.Arg462Pro)single nucleotide variantPathogenicrs121907903GRCh37Chr 11, 32413565: 32413565
6WT1NM_024426.4(WT1): c.1193G> A (p.Cys398Tyr)single nucleotide variantPathogenicrs121907904GRCh37Chr 11, 32417859: 32417859
7WT1NM_024426.4(WT1): c.1432+5G> Asingle nucleotide variantPathogenicrs587776576GRCh38Chr 11, 32391967: 32391967
8WT1NM_024426.4(WT1): c.1333C> T (p.His445Tyr)single nucleotide variantPathogenicrs28942089GRCh37Chr 11, 32414218: 32414218
9WT1NM_024426.4(WT1): c.1282T> G (p.Cys428Gly)single nucleotide variantPathogenicrs121907905GRCh37Chr 11, 32414269: 32414269
10WT1NM_024426.4(WT1): c.1288C> T (p.Arg430Ter)single nucleotide variantPathogenicrs121907906GRCh37Chr 11, 32414263: 32414263
11WT1NM_024426.4(WT1): c.1323C> G (p.His441Gln)single nucleotide variantPathogenicrs121907907GRCh37Chr 11, 32414228: 32414228

Copy number variations for Denys-Drash Syndrome from CNVD:

6
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
153562113100000036400000Copy numberWT1Denys-drash syndrome
253587113100000036400000Copy numberWT1Denys-drash syndrome

Expression for genes affiliated with Denys-Drash Syndrome

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Search GEO for disease gene expression data for Denys-Drash Syndrome.

Pathways for genes affiliated with Denys-Drash Syndrome

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GO Terms for genes affiliated with Denys-Drash Syndrome

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Cellular components related to Denys-Drash Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1slit diaphragmGO:00360579.6NPHS1, NPHS2

Biological processes related to Denys-Drash Syndrome according to GeneCards Suite gene sharing:

(show all 14)
idNameGO IDScoreTop Affiliating Genes
1metanephric epithelium developmentGO:007220710.3PAX2, WT1
2metanephric mesenchyme developmentGO:007207510.2PAX2, WT1
3mesenchymal to epithelial transitionGO:006023110.2PAX2, WT1
4glomerular basement membrane developmentGO:003283610.1NPHS1, WT1
5excretionGO:000758810.0NPHS1, NPHS2
6negative regulation of female gonad developmentGO:200019510.0NR5A1, WT1
7camera-type eye developmentGO:004301010.0PAX2, WT1
8branching involved in ureteric bud morphogenesisGO:00016589.7PAX2, WT1
9adrenal gland developmentGO:00303259.6NR5A1, WT1
10germ cell developmentGO:00072819.6BAX, WT1
11tissue developmentGO:00098889.6NR5A1, WT1
12response to woundingGO:00096119.4BAX, PDGFA
13positive regulation of male gonad developmentGO:20000209.2NR5A1, WT1
14male gonad developmentGO:00085849.0BAX, NR5A1, WT1

Sources for Denys-Drash Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet