MCID: FRS002
MIFTS: 49

Frasier Syndrome

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

Aliases & Classifications for Frasier Syndrome

MalaCards integrated aliases for Frasier Syndrome:

Name: Frasier Syndrome 54 38 12 50 24 25 56 71 29 13 52 42 14 69
Fs 25 71

Characteristics:

Orphanet epidemiological data:

56
frasier syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

54
Miscellaneous:
phenotypic overlap with denys-drash syndrome .

Inheritance:
somatic mutation
autosomal dominant


HPO:

32
frasier syndrome:
Inheritance autosomal dominant inheritance somatic mutation


Classifications:



External Ids:

OMIM 54 136680
Disease Ontology 12 DOID:0050438
MeSH 42 D052159
NCIt 47 C122805
SNOMED-CT 64 445431000
Orphanet 56 ORPHA347
MESH via Orphanet 43 D052159
UMLS via Orphanet 70 C0950122
ICD10 via Orphanet 34 N04.1
MedGen 40 C0950122
UMLS 69 C0950122

Summaries for Frasier Syndrome

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 347disease definitionfrasier syndrome is characterised by the association of male pseudohermaphrodism and glomerular nephropathy. this syndrome is associated with a high risk of developing gonadoblastoma.epidemiologyprevalence of this rare disease is unknown.clinical descriptionpatients with frasier syndrome present with normal female external genitalia and streak gonads, and have a 46,xy karyotype. nephropathy presents during childhood with proteinuria and nephrotic syndrome, and progresses to end-stage renal disease in adolescence or adulthood.etiologyheterozygousmutations in the wt1 gene have been found in women affected by frasier syndrome. the wt1 gene contains 10 exons and codes for a zinc-finger dna-binding protein. this protein plays an important role in renal and gonadal development. mutations responsible for frasier syndrome are located in intron 9, an alternative splicing site, and lead to the loss or haploinsufficiency of the wt1+kts isoform, a transcription factor.diagnostic methodshistologically, glomerular lesions are not specific. they consist of minimal glomerular lesions associated with segmental and focal glomerular hyalinosis. in women, the diagnosis may be made during investigation for primary amenorrhea, or, in some cases, after renal transplant when nephropathy has progressed to renal failure.visit the orphanet disease page for more resources. last updated: 2/14/2007

MalaCards based summary : Frasier Syndrome, also known as fs, is related to denys-drash syndrome and monostotic fibrous dysplasia, and has symptoms including nephrotic syndrome, focal segmental glomerulosclerosis and gonadal dysgenesis. An important gene associated with Frasier Syndrome is WT1 (Wilms Tumor 1), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Neural Stem Cell Differentiation Pathways and Lineage-specific Markers. Affiliated tissues include Kidney and kidney, and related phenotypes are cardiovascular system and homeostasis/metabolism

UniProtKB/Swiss-Prot : 71 Frasier syndrome: Characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant.

Genetics Home Reference : 25 Frasier syndrome is a condition that affects the kidneys and genitalia.

OMIM : 54
Frasier syndrome is a rare disorder defined by pseudohermaphroditism and progressive glomerulopathy (Frasier et al., 1964; Haning et al., 1985; Kinberg et al., 1987). Patients present with normal female external genitalia, streak gonads, and XY karyotype, and frequently develop gonadoblastoma (Blanchet et al., 1977). Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by nonspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood. Wilms tumor is not a usual feature (Barbaux et al., 1997). (136680)

Wikipedia : 72 Frasier syndrome is a urogenital anomaly associated with the WT1 (Wilms tumor 1 gene)... more...

Related Diseases for Frasier Syndrome

Diseases related to Frasier Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 52)
id Related Disease Score Top Affiliating Genes
1 denys-drash syndrome 10.9
2 monostotic fibrous dysplasia 10.7 CD2AP NPHS2
3 renal hypoplasia 10.7 NPHS1 NPHS2
4 pfeiffer syndrome type 2 10.7 PLCE1 WT1
5 anterior spinal artery stroke 10.6 NR5A1 SRY
6 hydronephrosis, congenital, with cleft palate, characteristic facies, hypotonia, and mental retardation 10.5 SOX9 SRY WT1
7 cardiomyopathy, dilated, 1ee 10.5 CD2AP NPHS1 NPHS2
8 spermatogenic failure, y-linked, 1 10.5 NR5A1 SOX9 SRY
9 46xy sex reversal 8 10.5 ACTN4 NPHS1 NPHS2
10 renal dysplasia 10.5 NPHS1 PLCE1 WT1
11 spastic monoplegia 10.5 CD2AP NPHS1 NPHS2
12 exocrine pancreatic insufficiency 10.4 NPHS1 NPHS2 WT1
13 nasopharyngeal carcinoma 2 10.4 CD2AP NPHS1 NPHS2
14 sarcocystosis 10.4 NPHS1 NPHS2
15 brucella melitensis brucellosis 10.4 AMH SOX9 SRY
16 epileptic encephalopathy, early infantile, 31 10.4 PAX6 WT1
17 thymus mucoepidermoid carcinoma 10.4 AMH SRY
18 corneal dystrophy, fuchs endothelial, 8 10.4 ACTN4 NPHS2
19 wrinkles 10.4 PAX6 SRY WT1
20 idiopathic recurrent pericarditis 10.3 NR5A1 SOX9 SRY WT1
21 vaginal discharge 10.3 SOX9 SRY
22 farmer's lung 10.3 NR5A1 SOX9 SRY WT1
23 tooth disease 10.3 NR5A1 SOX9 SRY WT1
24 lymphoepithelioma-like carcinoma 10.3 CD2AP PAX6
25 capillary lymphangioma 10.3 AMH NR5A1 SRY
26 avoidant personality disorder 10.2 AMH NR5A1 SRY
27 adrenoleukodystrophy 10.2 AMH NR5A1 WT1
28 congenital pulmonary alveolar proteinosis 10.1 ACTN4 CD2AP NPHS1 NPHS2 WT1
29 gonadoblastoma 10.1
30 inhibited male orgasm 10.1 ACTN4 CD2AP NPHS1 NPHS2 WT1
31 gonadal dysgenesis 10.1
32 multiple synostoses syndrome 10.0 AMH NR5A1 SOX9 SRY WT1
33 female stress incontinence 9.8 ACTN4 CD2AP NPHS1 NPHS2 PLCE1 WT1
34 hyperferritinemia-cataract syndrome 9.8 ACTN4 CD2AP NPHS1 NPHS2 PLCE1 WT1
35 transient refractive change 9.8 ACTN4 CD2AP NPHS1 NPHS2 PLCE1 WT1
36 gas gangrene 9.8 ACTN4 CD2AP NPHS1 NPHS2 PLCE1 WT1
37 digestive system melanoma 9.8 NPHS1 NPHS2 PDGFA PLCE1 WT1
38 46 xy gonadal dysgenesis 9.7
39 astrocytoma 9.7
40 sertoli cell tumor 9.7
41 seminoma 9.7
42 pilocytic astrocytoma 9.7
43 alport syndrome 9.7
44 end stage renal failure 9.7
45 focal segmental glomerulosclerosis 9.7
46 nephronophthisis 9.7
47 amenorrhea 9.7
48 diabetes mellitus, insulin-resistant, with acanthosis nigricans 9.7 AMH NR5A1 WT1
49 46 xx gonadal dysgenesis 9.7 AMH FGF9 NR5A1 SOX9 SRY WT1
50 nephrotic syndrome, type 4 9.6 CD2AP NPHS1 NPHS2 NR5A1 PDGFA WT1

Graphical network of the top 20 diseases related to Frasier Syndrome:



Diseases related to Frasier Syndrome

Symptoms & Phenotypes for Frasier Syndrome

Symptoms via clinical synopsis from OMIM:

54

Neoplasia:
gonadoblastoma

Genitourinary- Kidneys:
focal and segmental glomerular sclerosis
nephrotic syndrome
chronic renal failure

Genitourinary- Internal Genitalia Male:
gonadoblastoma
pure gonadal dysgenesis

Endocrine Features:
primary amenorrhea

Genitourinary- Internal Genitalia Female:
gonadoblastoma
pure gonadal dysgenesis

Genitourinary- External Genitalia Male:
male pseudohermaphroditism


Clinical features from OMIM:

136680

Human phenotypes related to Frasier Syndrome:

32 (show all 7)
id Description HPO Frequency HPO Source Accession
1 nephrotic syndrome 32 HP:0000100
2 focal segmental glomerulosclerosis 32 HP:0000097
3 gonadal dysgenesis 32 HP:0000133
4 primary amenorrhea 32 HP:0000786
5 male pseudohermaphroditism 32 HP:0000037
6 stage 5 chronic kidney disease 32 HP:0003774
7 ovarian gonadoblastoma 32 HP:0000149

MGI Mouse Phenotypes related to Frasier Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.18 ACTN4 CD2AP FGF9 NPHS2 NR5A1 PAX6
2 homeostasis/metabolism MP:0005376 10.18 ACTN4 AMH CD2AP FGF9 LHX9 NPHS1
3 growth/size/body region MP:0005378 10.14 ACTN4 CD2AP FGF9 LHX9 NPHS2 NR5A1
4 mortality/aging MP:0010768 10.1 ACTN4 CD2AP CMIP FGF9 NPHS1 NPHS2
5 endocrine/exocrine gland MP:0005379 10.03 NR5A1 PAX6 SOX9 WT1 AMH CD2AP
6 embryo MP:0005380 9.85 WT1 NR5A1 PAX6 PDGFA SOX9
7 muscle MP:0005369 9.73 PAX6 PDGFA PLCE1 SOX9 WT1 FGF9
8 renal/urinary system MP:0005367 9.56 ACTN4 CD2AP NPHS1 NPHS2 PAX6 PDGFA
9 neoplasm MP:0002006 9.46 AMH PAX6 PLCE1 WT1
10 reproductive system MP:0005389 9.23 AMH FGF9 LHX9 NR5A1 PAX6 PDGFA

Drugs & Therapeutics for Frasier Syndrome

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases Completed NCT01252901
2 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Frasier Syndrome

Cochrane evidence based reviews: frasier syndrome

Genetic Tests for Frasier Syndrome

Genetic tests related to Frasier Syndrome:

id Genetic test Affiliating Genes
1 Frasier Syndrome 29 24 WT1

Anatomical Context for Frasier Syndrome

MalaCards organs/tissues related to Frasier Syndrome:

39
Kidney
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Frasier Syndrome:
id Tissue Anatomical CompartmentCell Relevance
1 Kidney Metanephric Mesenchyme Metanephric Mesenchyme Cells Affected by disease

Publications for Frasier Syndrome

Articles related to Frasier Syndrome:

(show all 46)
id Title Authors Year
1
Laparoscopically Removed Streak Gonad Revealed Gonadoblastoma in Frasier Syndrome. ( 28668903 )
2017
2
Gonadal Tumor in Frasier Syndrome: A Review and Classification. ( 25623218 )
2015
3
Total Laparoscopic Colocolpopoiesis in a Kidney transplant Recipient With Frasier Syndrome. ( 26516816 )
2015
4
Proteinuria in Frasier syndrome. ( 24364235 )
2013
5
Frasier syndrome: four new cases with unusual presentations. ( 23295293 )
2012
6
Sertoli cell tumor and gonadoblastoma in an untreated 29-year-old 46,XY phenotypic male with Frasier syndrome carrying a WT1 IVS9+4C>T mutation. ( 22908070 )
2012
7
Frasier syndrome in 17-year-old girl--case report. ( 21853939 )
2011
8
Recurrence of a dysgerminoma in Frasier syndrome. ( 20408995 )
2011
9
Frasier syndrome: early gonadoblastoma and cyclosporine responsiveness. ( 20419325 )
2010
10
Frasier syndrome, a potential cause of end-stage renal failure in childhood. ( 19921279 )
2010
11
A female infant with Frasier syndrome showing splice site mutation in Wilms' tumor gene (WT1) intron 9. ( 20497763 )
2010
12
[WT1 mutation as a cause of progressive nephropathy in Frasier syndrome--case report]. ( 19711733 )
2009
13
Bilateral gonadoblastoma with dysgerminoma and pilocytic astrocytoma with WT1 GT-IVS9 mutation: A 46 XY phenotypic female with Frasier syndrome. ( 19653292 )
2009
14
Expanding the clinical spectrum of Frasier syndrome. ( 17378674 )
2008
15
Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndrome. ( 18271004 )
2008
16
WT1 mutation and podocyte molecular expression in a Chinese Frasier syndrome patient. ( 17694336 )
2007
17
Lack of puberty despite elevated estradiol in a 46,XY phenotypic female with Frasier syndrome. ( 16717397 )
2006
18
Frasier syndrome: a rare cause of delayed puberty. ( 16760553 )
2006
19
Frasier syndrome in a pre-menarchal girl: laparoscopic resection of gonadoblastoma. ( 16915373 )
2006
20
[Frasier syndrome: a rare syndrome with WT1 gene mutation in pediatric urology]. ( 16440249 )
2006
21
Prophylactic bilateral salpingo-oopherectomy in a 17-year-old with Frasier syndrome reveals gonadoblastoma and seminoma: a case report. ( 17101338 )
2006
22
Frasier syndrome comes full circle: genetic studies performed in an original patient. ( 15973330 )
2005
23
46, XY gonadal dysgenesis and chronic renal failure: first reported case with Frasier syndrome from Turkey. ( 15658629 )
2004
24
Twenty-eight-year-old female with primary amenorrhea and chronic renal failure: a case of Frasier syndrome? ( 14977287 )
2004
25
WT1 gene mutation responsible for male sex reversal and renal failure: the Frasier syndrome. ( 12932885 )
2003
26
Gonad development in Drash and Frasier syndromes depends on WT1 mutations. ( 15357247 )
2003
27
Alport syndrome-like basement membrane changes in Frasier syndrome: an electron microscopy study. ( 12722046 )
2003
28
Molecular analysis of Frasier syndrome: mutation in the WT1 gene in a girl with gonadal dysgenesis and nephronophthisis. ( 12199335 )
2002
29
An unusual phenotype of Frasier syndrome due to IVS9 +4C>T mutation in the WT1 gene: predominantly male ambiguous genitalia and absence of gonadal dysgenesis. ( 12050205 )
2002
30
A girl with bilateral ovarian tumours: Frasier syndrome. ( 11954756 )
2002
31
Gonadoblastoma and dysgerminoma associated with XY gonadal dysgenesis in an adolescent with chronic renal failure: a case of Frasier syndrome. ( 12106750 )
2002
32
Gonadal mosaicism of Frasier syndrome in 3 Chinese siblings with donor splice site mutation of Wilms' tumour gene. ( 12119492 )
2002
33
Frasier syndrome with childhood-onset renal failure. ( 11509863 )
2001
34
Clinical spectrum of Denys-Drash and Frasier syndrome. ( 11354777 )
2001
35
Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy? ( 10762296 )
2000
36
Absent pubertal development in a child with chronic renal failure: the case of Frasier syndrome. ( 11007843 )
2000
37
A Japanese case with Frasier syndrome caused by the splice junction mutation of WT1 gene. ( 10670748 )
1999
38
The same mutation affecting the splicing of WT1 gene is present on Frasier syndrome patients with or without Wilms' tumor. ( 10094551 )
1999
39
Frasier syndrome: a cause of focal segmental glomerulosclerosis in a 46,XX female. ( 10505699 )
1999
40
Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome. ( 10571943 )
1999
41
Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome? ( 9475094 )
1998
42
Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms. ( 9499425 )
1998
43
Donor splice-site mutations in WT1 are responsible for Frasier syndrome. ( 9398852 )
1997
44
Frasier syndrome. ( 15251548 )
1996
45
Distinct molecular origins for Denys-Drash and Frasier syndromes. ( 8386697 )
1993
46
Molecular analysis of the sex-determining region from the Y chromosome in two patients with Frasier syndrome. ( 1478624 )
1992

Variations for Frasier Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Frasier Syndrome:

71
id Symbol AA change Variation ID SNP ID
1 WT1 p.Phe392Leu VAR_015060

ClinVar genetic disease variations for Frasier Syndrome:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 WT1 NM_001198551.1(WT1): c.787+15T> A single nucleotide variant Pathogenic rs587776575 GRCh38 Chromosome 11, 32391966: 32391966
2 WT1 NM_024426.4(WT1): c.1384C> T (p.Arg462Trp) single nucleotide variant Pathogenic rs121907900 GRCh37 Chromosome 11, 32413566: 32413566
3 WT1 NM_024426.4(WT1): c.1432+5G> A single nucleotide variant Pathogenic rs587776576 GRCh38 Chromosome 11, 32391967: 32391967
4 WT1 NM_024426.4(WT1): c.1372C> T (p.Arg458Ter) single nucleotide variant Pathogenic rs121907909 GRCh37 Chromosome 11, 32413578: 32413578
5 WT1 NM_024426.4(WT1): c.1432+4C> T single nucleotide variant Pathogenic rs587776577 GRCh38 Chromosome 11, 32391968: 32391968
6 WT1 NM_024426.4(WT1): c.1378T> C (p.Phe460Leu) single nucleotide variant Pathogenic rs28941779 GRCh37 Chromosome 11, 32413572: 32413572
7 WT1 NM_001198551.1(WT1): c.161delC (p.Pro54Argfs) deletion Pathogenic rs1060501253 GRCh38 Chromosome 11, 32428031: 32428031

Copy number variations for Frasier Syndrome from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 53589 11 31000000 36400000 Copy number WT1 Frasier syndrome

Expression for Frasier Syndrome

Search GEO for disease gene expression data for Frasier Syndrome.

Pathways for Frasier Syndrome

GO Terms for Frasier Syndrome

Cellular components related to Frasier Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 slit diaphragm GO:0036057 8.62 NPHS1 NPHS2

Biological processes related to Frasier Syndrome according to GeneCards Suite gene sharing:

(show all 21)
id Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.96 NR5A1 PAX6 SOX9 SRY WT1
2 regulation of transcription from RNA polymerase II promoter GO:0006357 9.95 NR5A1 PAX6 SOX9 SRY WT1
3 cell differentiation GO:0030154 9.95 AMH FGF9 NR5A1 PAX6 SOX9 SRY
4 cell-cell signaling GO:0007267 9.88 AMH FGF9 NR5A1 PDGFA
5 positive regulation of gene expression GO:0010628 9.85 AMH FGF9 NR5A1 PAX6 SOX9
6 female gonad development GO:0008585 9.6 LHX9 NR5A1
7 sex differentiation GO:0007548 9.59 AMH SRY
8 adrenal gland development GO:0030325 9.58 NR5A1 WT1
9 tissue development GO:0009888 9.57 NR5A1 WT1
10 gonad development GO:0008406 9.54 AMH WT1
11 glomerular basement membrane development GO:0032836 9.52 NPHS1 WT1
12 glomerulus development GO:0032835 9.51 PLCE1 WT1
13 positive regulation of mesenchymal cell proliferation GO:0002053 9.5 FGF9 PDGFA SOX9
14 lacrimal gland development GO:0032808 9.49 PAX6 SOX9
15 regulation of timing of cell differentiation GO:0048505 9.48 FGF9 PAX6
16 positive regulation of epithelial cell differentiation GO:0030858 9.43 PAX6 SOX9
17 male sex determination GO:0030238 9.43 FGF9 SOX9 SRY
18 negative regulation of female gonad development GO:2000195 9.37 NR5A1 WT1
19 male gonad development GO:0008584 9.35 FGF9 LHX9 NR5A1 SOX9 WT1
20 sex determination GO:0007530 9.33 AMH NR5A1 WT1
21 positive regulation of male gonad development GO:2000020 8.92 NR5A1 SOX9 SRY WT1

Molecular functions related to Frasier Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 transcription factor activity, sequence-specific DNA binding GO:0003700 9.73 NR5A1 PAX6 SOX9 SRY WT1 ZNF274
2 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0003705 9.13 NR5A1 SOX9 SRY
3 sequence-specific DNA binding GO:0043565 9.1 LHX9 NR5A1 PAX6 SOX9 WT1 ZNF274
4 protein binding GO:0005515 10.03 ACTN4 CD2AP CMIP LHX9 NPHS1 NPHS2

Sources for Frasier Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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