WFS
MCID: WLF004
MIFTS: 69

Wolfram Syndrome (WFS) malady

Genetic diseases, Rare diseases, Eye diseases, Endocrine diseases, Ear diseases categories

Summaries for Wolfram Syndrome

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9Disease Ontology, 44NIH Rare Diseases, 66Wikipedia, 48OMIM, 34MalaCards
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NIH Rare Diseases:44 Wolfram syndrome, which is also known by the acronym didmoad, is characterized by diabetes insipidus (di); childhood-onset diabetes mellitus (dm); a gradual loss of vision caused by optic atrophy (oa); and deafness (d). other complications that affect the bladder and nervous system may also occur. mutations in two genes have been associated with wolfram syndrome. the majority of cases are associated with mutations in the wfs1 gene. mutations in the cisd2 gene have been identified in three consanguineous families of jordanian descent. the condition is inherited in an autosomal recessive manner. treatment is symptomatic and supportive. last updated: 9/8/2011

MalaCards: Wolfram Syndrome, also known as didmoad syndrome, is related to wolfram syndrome 2 and waterhouse-friderichsen syndrome, and has symptoms including ophthalmoplegia/ophthalmoparesis/oculomotor palsy, anaemia and cardiomyopathy/hypertrophic/dilated. An important gene associated with Wolfram Syndrome is WFS1 (Wolfram syndrome 1 (wolframin)), and among its related pathways are PERK regulated gene expression and Protein processing in endoplasmic reticulum. The compounds methylphenidate and pramipexole have been mentioned in the context of this disorder. Affiliated tissues include eye, lung and brain, and related mouse phenotypes are vision/eye and endocrine/exocrine gland.

Disease Ontology:9 A genetic disease that is characterized by diabetes mellitus, optic atrophy, and deafness as well as various other possible disorders and has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the gene encoding wolframin (wfs1).

Wikipedia:66 Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and... more...

Description from OMIM:48 222300,604928,598500

Aliases & Classifications for Wolfram Syndrome

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44NIH Rare Diseases, 9Disease Ontology, 10diseasecard, 21GeneTests, 23GTR, 22Genetics Home Reference, 48OMIM, 11DISEASES, 46Novoseek, 50Orphanet, 63UMLS, 36MeSH, 59SNOMED-CT, 41NCIt, 37MESH via Orphanet, 27ICD10 via Orphanet, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet
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Classifications:



Characteristics (Orphanet epidemiological data):

50
wolfram syndrome:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000; Age of onset: Childhood; Age of death: Adult


Aliases & Descriptions:

wolfram syndrome 9 10 44 21 23 22 48 11 46 50 63
didmoad syndrome 44 22 50
didmoad 9 44 22
diabetes mellitus and insipidus with optic atrophy and deafness 9 23
diabetes insipidus and mellitus with optic atrophy and deafness 44 22
diabetes insipidus, diabetes mellitus, optic atrophy, and deafness 22
diabetes insipidus - diabetes mellitus - optic atrophy - deafness 50
didmoadud 22
wfs 44


External Ids:

Disease Ontology9 DOID:10632
MeSH36 D014929
NCIt41 C35133
SNOMED-CT59 70694009
MESH via Orphanet37 D014929
ICD10 via Orphanet27 E10.7, H48.0
SNOMED-CT via Orphanet60 70694009
UMLS via Orphanet64 C0043207

Related Diseases for Wolfram Syndrome

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18GeneCards, 19GeneDecks
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Graphical network of the top 20 diseases related to Wolfram Syndrome:



Diseases related to wolfram syndrome

Symptoms for Wolfram Syndrome

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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

222300

Clinical features from OMIM:

222300,604928,598500

Symptoms:

50 (show all 36)
  • ophthalmoplegia/ophthalmoparesis/oculomotor palsy
  • anaemia
  • cardiomyopathy/hypertrophic/dilated
  • myopathy
  • late puberty/hypogonadism/hypogenitalism
  • diabetes insipidus
  • peripheral neuropathy
  • recurrent urinary infections
  • gastrointestinal bleeding/hemorrhage/hematemesis/melena/rectorrhagia
  • psychosis/schizophrenia/maniac disorder
  • glaucoma
  • epigastralgia/heartburn/gastric/duodenal ulcer/gastritis
  • bladder and ureter anomalies
  • nystagmus
  • renal disease/nephropathy
  • sensorineural deafness/hearing loss
  • optic nerve anomaly/optic atrophy/anomaly of the papilla
  • elocution disorders/dysarthria/dysphonia
  • ataxia/incoordination/trouble of the equilibrium
  • constipation
  • feeding disorder/dysphagia/swallowing/sucking disorder/esophageal dyskinesia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • sleep and vigilance disorders
  • seizures/epilepsy/absences/spasms/status epilepticus
  • cortical atrophy without hydrocephaly/cerebral hemiatrophy/subcortical atrophy
  • autosomal dominant inheritance
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • restricted joint mobility/joint stiffness/ankylosis
  • malabsorption/chronic diarrhea/steatorrhea
  • delirium/hallucination
  • psychic/behavioural troubles
  • early death/lethality
  • psychic/psychomotor regression/dementia/intellectual decline
  • dysautonomia/autonomous nervous sytem anomalies
  • diabetes mellitus
  • autosomal recessive inheritance

Drugs & Therapeutics for Wolfram Syndrome

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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-RT
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Approved drugs:

Search CenterWatch for Wolfram Syndrome

Drug clinical trials:

Search ClinicalTrials for Wolfram Syndrome

Search NIH Clinical Center for Wolfram Syndrome

Search CenterWatch for Wolfram Syndrome

Genetic Tests for Wolfram Syndrome

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21GeneTests, 23GTR
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Genetic tests related to Wolfram Syndrome:

id Genetic test Affiliating Genes
1 Wolfram Syndrome21 23 WFS1
2 Diabetes Mellitus and Insipidus with Optic Atrophy and Deafness23

Anatomical Context for Wolfram Syndrome

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34MalaCards
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MalaCards organs/tissues related to Wolfram Syndrome:

34
Eye, Lung, Brain, Pancreas, Kidney, Hypothalamus

Animal Models for Wolfram Syndrome or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Wolfram Syndrome:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053918.5TH, CISD2, EFEMP1, DRD5
2MP:00053798.5DRD5, WFS1, EFEMP1, CISD2, TH
3MP:00053678.3DRD5, EFEMP1, CISD2, HSPA5
4MP:00028738.2DRD5, EFEMP1, HSPA5, TH
5MP:00107718.1TH, HSPA5, CISD2, EFEMP1, WFS1
6MP:00053857.9TH, HSPA5, CISD2, EFEMP1, DRD5
7MP:00053787.6TH, HSPA5, CISD2, EFEMP1, WFS1
8MP:00053767.4TH, ATF6, HSPA5, CISD2, EFEMP1, WFS1
9MP:00107687.3TH, ATF6, HSPA5, CISD2, EFEMP1, WFS1

Publications for Wolfram Syndrome

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53PubMed
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Articles related to Wolfram Syndrome:

(show top 50)    (show all 194)
idTitleAuthorsYear
1
EURO-WABB: an EU rare diseases registry for Wolfram syndrome, AlstrAPm syndrome and Bardet-Biedl syndrome. (23981649)
2013
2
Audiologic and vestibular findings in Wolfram syndrome. (23698626)
2013
3
Vacuolar-type H+-ATPase V1A subunit is a molecular partner of Wolfram syndrome 1 (WFS1) protein, which regulates its expression and stability. (23035048)
2013
4
Expansion of the clinical ocular spectrum of Wolfram Syndrome in a family carrying a novel WFS1 gene deletion. (23373429)
2013
5
Molecular characterization of WFS1 in an Iranian family with Wolfram syndrome reveals a novel frameshift mutation associated with early symptoms. (23845777)
2013
6
Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro). (21968327)
2012
7
Cataract as a phenotypic marker for a mutation in WFS1, the Wolfram syndrome gene. (21623591)
2012
8
Wolfram syndrome: new mutations, different phenotype. (22238590)
2012
9
A new structural rearrangement associated to Wolfram syndrome in a child with a partial phenotype. (22771918)
2012
10
Wolfram Syndrome: a rare optic neuropathy in youth with type 1 diabetes. (21892113)
2011
11
Neurologic features and genotype-phenotype correlation in Wolfram syndrome. (21446023)
2011
12
Neuropathy in Wolfram syndrome. (20888932)
2011
13
The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA deletions in a patient with Wolfram syndrome and cardiomyopathy. (21723259)
2011
14
Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and determines granule acidification in pancreatic beta-cells. (21199859)
2011
15
Premature coronary artery disease in a patient with Wolfram syndrome. (21501987)
2011
16
A case of wolfram syndrome. (22737327)
2010
17
Congenital cataracts in two siblings with Wolfram syndrome. (21067485)
2010
18
Expression and localization of Wolfram syndrome 1 gene in the developing rat pancreas. (19916172)
2009
19
Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome. (19042979)
2009
20
Wolfram syndrome 1 (Wfs1) gene expression in the normal mouse visual system. (18613120)
2008
21
Psychiatric symptoms in a patient with Wolfram syndrome caused by a combination of thalamic deficit and endocrinological pathologies. (19090413)
2008
22
Wolfram syndrome. Clinical and genetic study in two families]. (18194629)
2008
23
Distribution of Wfs1 protein in the central nervous system of the mouse and its relation to clinical symptoms of the Wolfram syndrome. (18551525)
2008
24
A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. (17846994)
2007
25
Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): an age- and duration-matched comparison with common type 1 diabetes. (17536072)
2007
26
Wolfram syndrome: case report and review of the literature. (17914206)
2007
27
Bowel dysfunction in Wolfram syndrome. (16443921)
2006
28
Atrioventricular nodal reentrant tachycardia in two siblings with Wolfram syndrome. (16948749)
2006
29
Imaging characteristics of familial Wolfram syndrome. (15765170)
2005
30
Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified. (16151413)
2005
31
Identification of a novel WFS1 mutation (AFF344-345ins) in Japanese patients with Wolfram syndrome. (16005363)
2005
32
Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene. (15605410)
2005
33
Solitary pancreas transplantation in Wolfram syndrome. (14657707)
2003
34
Bleeding tendency in Wolfram syndrome: a newly identified feature with phenotype genotype correlation. (11317648)
2001
35
Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. (11260218)
2001
36
Mutational analysis of the Wolfram syndrome gene in two families with chromosome 4p-linked bipolar affective disorder. (10893488)
2000
37
Partial Wolfram syndrome (DIDMOAD): two new patients in a family. Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. (10480791)
1999
38
Role of early fundoscopy for diagnosis of Wolfram syndrome in type 1 diabetic patients. (10480790)
1999
39
Predisposition of Wolfram syndrome heterozygotes to psychiatric illness. (9491819)
1998
40
Psychiatric disorders in Wolfram syndrome heterozygotes. (9491807)
1998
41
Autosomal recessive Wolfram syndrome associated with an 8.5-kb mtDNA single deletion. (8651280)
1996
42
Mitochondrial mutation commonly associated with Leber's hereditary optic neuropathy observed in a patient with Wolfram syndrome (DIDMOAD). (8071960)
1994
43
Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4. (7987399)
1994
44
Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300). (8383698)
1993
45
Successful pregnancy in two sisters with Wolfram syndrome. (8444596)
1993
46
Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy and deafness (DIDMOAD, Wolfram syndrome). (7609443)
1993
47
A Chinese family with Wolfram syndrome presenting with rapidly progressing diabetic retinopathy and renal failure. (2221817)
1990
48
Primary hypogonadism in two siblings with Wolfram syndrome. (3677989)
1987
49
Optic atrophy in Wolfram syndrome. (3561950)
1986
50
Wolfram syndrome and HLA. (7366689)
1980

Variations for Wolfram Syndrome

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar), 8dbSNP
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UniProtKB/Swiss-Prot genetic disease variations for Wolfram Syndrome:

65 (show all 22)
id Symbol AA change Variation ID SNP ID
1WFS1p.Pro504LeuVAR_005842rs28937892
2WFS1p.Gly695ValVAR_005844rs28937891
3WFS1p.Pro724LeuVAR_005845rs28937890
4WFS1p.Glu169LysVAR_009109
5WFS1p.Pro292SerVAR_009110
6WFS1p.Ile296SerVAR_009111
7WFS1p.Gly437ArgVAR_009114
8WFS1p.Cys690ArgVAR_009116
9WFS1p.Trp700CysVAR_009117
10WFS1p.Gly736SerVAR_009118
11WFS1p.Pro885LeuVAR_009119
12WFS1p.Ala58ValVAR_011305
13WFS1p.Ala126ThrVAR_011306
14WFS1p.Ser443IleVAR_011308
15WFS1p.Gly780ArgVAR_011313
16WFS1p.Arg818CysVAR_011314rs35932623
17WFS1p.Ala133ThrVAR_014034
18WFS1p.Tyr669CysVAR_014038
19WFS1p.Tyr110AsnVAR_029499
20WFS1p.Arg457SerVAR_029502
21WFS1p.Arg629TrpVAR_029505rs71530910
22WFS1p.Arg558CysVAR_068343

Clinvar genetic disease variations for Wolfram Syndrome:

1 (show all 19)
id Gene Name Type Significance SNP ID Assembly Location
1WFS1NM_006005.3(WFS1): c.2119G> T (p.Val707Phe)single nucleotide variantPathogenicrs71524377GRCh37Chr 4, 6303641: 6303641
2WFS1WFS1, 8-BP DEL, NT2106deletionPathogenic
3WFS1NM_006005.3(WFS1): c.2051C> T (p.Ala684Val)single nucleotide variantPathogenicrs387906930GRCh37Chr 4, 6303573: 6303573
4WFS1WFS1, 3-BP DEL, VAL415DELdeletionPathogenic
5WFS1WFS1, 4-BP DEL, 1387CTCTdeletionPathogenic
6WFS1WFS1, 2-BP DEL, 2812TCdeletionPathogenic
7WFS1WFS1, 15-BP DEL, NT1685deletionPathogenic
8WFS1NM_006005.3(WFS1): c.2171C> T (p.Pro724Leu)single nucleotide variantPathogenicrs28937890GRCh37Chr 4, 6303693: 6303693
9WFS1NM_006005.3(WFS1): c.2084G> T (p.Gly695Val)single nucleotide variantPathogenicrs28937891GRCh37Chr 4, 6303606: 6303606
10WFS1NM_006005.3(WFS1): c.1944G> A (p.Trp648Ter)single nucleotide variantPathogenicrs104893879GRCh37Chr 4, 6303466: 6303466
11WFS1NM_006005.3(WFS1): c.1511C> T (p.Pro504Leu)single nucleotide variantPathogenicrs28937892GRCh37Chr 4, 6303033: 6303033
12WFS1WFS1, 7-BP INS, NT1610insertionPathogenic
13WFS1WFS1, 9-BP DEL, NT1380deletionPathogenic
14WFS1WFS1, 460, G-A, +1single nucleotide variantPathogenic
15WFS1NM_006005.3(WFS1): c.676C> T (p.Gln226Ter)single nucleotide variantPathogenicrs104893880GRCh37Chr 4, 6293688: 6293688
16WFS1NM_006005.3(WFS1): c.2455C> T (p.Gln819Ter)single nucleotide variantPathogenicrs104893881GRCh37Chr 4, 6303977: 6303977
17WFS1WFS1, 4-BP DEL, NT2648deletionPathogenic
18WFS1NM_006005.3(WFS1): c.409_424dup16 (p.Val142Glyfs)duplicationPathogenicGRCh37Chr 4, 6290807: 6290822
19WFS1WFS1, 16-BP DEL, NT1362deletionPathogenic

Expression for genes affiliated with Wolfram Syndrome

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Wolfram Syndrome

Search GEO for disease gene expression data for Wolfram Syndrome.

Pathways for genes affiliated with Wolfram Syndrome

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51PathCards, 56Reactome, 31KEGG, 39NCBI BioSystems Database
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Pathways related to Wolfram Syndrome according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.0HSPA5, ATF6
28.7WFS1, HSPA5, ATF6
3
Show member pathways
8.7WFS1, HSPA5, ATF6
4
Show member pathways
8.3ATF6, HSPA5, TOMM40, WFS1

Compounds for genes affiliated with Wolfram Syndrome

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46Novoseek, 52PharmGKB, 12DrugBank, 30IUPHAR, 25HMDB, 3BitterDB, 62Tocris Bioscience
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Compounds related to Wolfram Syndrome according to GeneCards/GeneDecks:

(show all 14)
idCompoundScoreTop Affiliating Genes
1methylphenidate46 52 1211.8DRD5, TH
2pramipexole46 30 52 1212.7TH, DRD5
3apomorphine30 46 1211.7DRD5, TH
4quetiapine46 52 30 25 1213.7DRD5, TH
5levodopa46 1210.6DRD5, TH
6clozapine46 30 52 1212.5TH, DRD5
7catecholamine469.5DRD5, TH
8trolox469.4TH, HSPA5
9haloperidol46 52 30 3 1213.2DRD5, TH
10tunicamycin46 6210.1HSPA5, ATF6
11iron46 259.9TH, HSPA5, CISD2
12dithiothreitol468.9HSPA5, ATF6
13dopamine46 30 25 1211.8DRD5, HSPA5, TH
14thapsigargin46 629.8HSPA5, ATF6, TH

GO Terms for genes affiliated with Wolfram Syndrome

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17Gene Ontology
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Cellular components related to Wolfram Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1integral component of endoplasmic reticulum membraneGO:0301769.0WFS1, HSPA5
2endoplasmic reticulumGO:0057838.9WFS1, CISD2, HSPA5
3endoplasmic reticulum membraneGO:0057898.2WFS1, CISD2, HSPA5, ATF6

Biological processes related to Wolfram Syndrome according to GeneCards/GeneDecks:

(show all 11)
idNameGO IDScoreTop Affiliating Genes
1multicellular organismal agingGO:0102599.7CISD2, TH
2synaptic transmission, dopaminergicGO:0019639.6TH, DRD5
3sensory perception of soundGO:0076059.6WFS1, TH
4ER overload responseGO:0069839.5HSPA5, WFS1
5response to amphetamineGO:0019759.5TH, DRD5
6ER-associated ubiquitin-dependent protein catabolic processGO:0304339.2WFS1, HSPA5
7visual perceptionGO:0076019.2WFS1, EFEMP1, TH
8positive regulation of protein ubiquitinationGO:0313989.0WFS1, HSPA5
9activation of signaling protein activity involved in unfolded protein responseGO:0069878.9WFS1, HSPA5, ATF6
10endoplasmic reticulum unfolded protein responseGO:0309688.9WFS1, HSPA5, ATF6
11cellular protein metabolic processGO:0442678.5WFS1, TOMM40, HSPA5, ATF6

Molecular functions related to Wolfram Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1dopamine bindingGO:0352409.5DRD5, TH

Products for genes affiliated with Wolfram Syndrome

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Sources for Wolfram Syndrome

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet