WFS
MCID: WLF004
MIFTS: 61

Wolfram Syndrome (WFS)

Categories: Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Wolfram Syndrome

MalaCards integrated aliases for Wolfram Syndrome:

Name: Wolfram Syndrome 12 73 20 43 58 36 29 54 6 44 15 39 70
Didmoad Syndrome 20 43 58 6
Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness 20 43
Didmoad 20 43
Diabetes Insipidus-Diabetes Mellitus-Optic Atrophy-Hearing Loss Syndrome 58
Diabetes Insipidus-Diabetes Mellitus-Optic Atrophy-Deafness Syndrome 58
Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness 43
Didmoadud 43
Wfs 20

Characteristics:

Orphanet epidemiological data:

58
wolfram syndrome
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (United Kingdom),1-9/1000000 (India),1-9/1000000 (Worldwide),1-9/100000,1-9/1000000 (Japan),1-9/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood; Age of death: adult;

Classifications:

Orphanet: 58  
Rare eye diseases
Rare otorhinolaryngological diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Wolfram Syndrome

MedlinePlus Genetics : 43 Wolfram syndrome is a condition that affects many of the body's systems. The hallmark features of Wolfram syndrome are high blood sugar levels resulting from a shortage of the hormone insulin (diabetes mellitus) and progressive vision loss due to degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). People with Wolfram syndrome often also have pituitary gland dysfunction that results in the excretion of excessive amounts of urine (diabetes insipidus), hearing loss caused by changes in the inner ear (sensorineural deafness), urinary tract problems, reduced amounts of the sex hormone testosterone in males (hypogonadism), or neurological or psychiatric disorders.Diabetes mellitus is typically the first symptom of Wolfram syndrome, usually diagnosed around age 6. Nearly everyone with Wolfram syndrome who develops diabetes mellitus requires insulin replacement therapy. Optic atrophy is often the next symptom to appear, usually around age 11. The first signs of optic atrophy are loss of color vision and side (peripheral) vision. Over time, the vision problems get worse, and people with optic atrophy are usually blind within approximately 8 years after signs of optic atrophy first begin.In diabetes insipidus, the pituitary gland, which is located at the base of the brain, does not function normally. This abnormality disrupts the release of a hormone called vasopressin, which helps control the body's water balance and urine production. Approximately 70 percent of people with Wolfram syndrome have diabetes insipidus. Pituitary gland dysfunction can also cause hypogonadism in males. The lack of testosterone that occurs with hypogonadism affects growth and sexual development. About 65 percent of people with Wolfram syndrome have sensorineural deafness that can range in severity from deafness beginning at birth to mild hearing loss beginning in adolescence that worsens over time. Sixty to 90 percent of people with Wolfram syndrome have a urinary tract problem. Urinary tract problems include obstruction of the ducts between the kidneys and bladder (ureters), a large bladder that cannot empty normally (high-capacity atonal bladder), disrupted urination (bladder sphincter dyssynergia), and difficulty controlling the flow of urine (incontinence).About 60 percent of people with Wolfram syndrome develop a neurological or psychiatric disorder, most commonly problems with balance and coordination (ataxia), typically beginning in early adulthood. Other neurological problems experienced by people with Wolfram syndrome include irregular breathing caused by the brain's inability to control breathing (central apnea), loss of the sense of smell, loss of the gag reflex, muscle spasms (myoclonus), seizures, reduced sensation in the lower extremities (peripheral neuropathy), and intellectual impairment. Psychiatric disorders associated with Wolfram syndrome include psychosis, episodes of severe depression, and impulsive and aggressive behavior.There are two types of Wolfram syndrome with many overlapping features. The two types are differentiated by their genetic cause. In addition to the usual features of Wolfram syndrome, individuals with Wolfram syndrome type 2 have stomach or intestinal ulcers and excessive bleeding after an injury. The tendency to bleed excessively combined with the ulcers typically leads to abnormal bleeding in the gastrointestinal system. People with Wolfram syndrome type 2 do not develop diabetes insipidus.Wolfram syndrome is often fatal by mid-adulthood due to complications from the many features of the condition, such as health problems related to diabetes mellitus or neurological problems.

MalaCards based summary : Wolfram Syndrome, also known as didmoad syndrome, is related to wolfram syndrome 2 and wolfram-like syndrome, autosomal dominant, and has symptoms including seizures, ataxia and tremor. An important gene associated with Wolfram Syndrome is WFS1 (Wolframin ER Transmembrane Glycoprotein), and among its related pathways/superpathways are Protein processing in endoplasmic reticulum and Glucose / Energy Metabolism. The drugs Acetylcysteine and Metformin have been mentioned in the context of this disorder. Affiliated tissues include eye, pituitary and brain, and related phenotypes are diabetes mellitus and sensorineural hearing impairment

Disease Ontology : 12 A syndrome that is characterized by diabetes mellitus, optic atrophy, and deafness.

GARD : 20 Wolfram syndrome, which is also known by the acronym DIDMOAD, is an inherited condition characterized by diabetes insipidus (DI), childhood-onset diabetes mellitus (DM), a gradual loss of vision caused by optic atrophy (OA), and deafness (D). Other symptoms may include bladder and bowel dysfunction, problems with the parts of the inner ear and brain that help control balance and eye movements (vestibular deficits), temperature regulation problems, decreased balance, uncoordinated (ataxic) gait and olfactory deficits. Also, psychiatric symptoms such as anxiety and depression have also been noted in some cases. There are two types of Wolfram syndrome (type 1 and type 2) which are primarily differentiated by their genetic cause. Type 1 is caused by changes ( mutations ) in the WFS1 gene, while type 2 is caused by mutations in the CISD2 gene. Both forms are inherited in an autosomal recessive manner. However, some cases of Wolfram syndrome type 1 have an autosomal dominant inheritance and are more severe. Diagnosis is suspected in cases of childhood-onset diabetes mellitus and optic atrophy, and this visual impairment is not due to the diabetes. Treatment is symptomatic and supportive.

KEGG : 36 Wolfram syndrome (WFS) is a rare hereditary neurodegenerative disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Two different categories of WFS (WFS1 and 2) are recognized, each with its own subset of variable symptoms, and resulting from mutations in the WFS1 and CISD2 genes, respectively. The WFS1 encodes an endoplasmic reticulum membrane-embedded protein. ERIS, the protein that CISD2 encodes, also localizes to the endoplasmic reticulum.

Wikipedia : 73 Wolfram syndrome, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and... more...

Related Diseases for Wolfram Syndrome

Diseases in the Wolfram Syndrome family:

Wolfram Syndrome 1 Wolfram Syndrome 2
Wolfram-Like Syndrome, Autosomal Dominant Autosomal Dominant Wolfram Syndrome

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

(show top 50) (show all 189)
# Related Disease Score Top Affiliating Genes
1 wolfram syndrome 2 33.0 WFS1 SLC9B1 CISD3 CISD2 CISD1
2 wolfram-like syndrome, autosomal dominant 32.6 WFS1 HERC2
3 wolfram syndrome 1 32.6 WFS1 TH SYVN1 HSPA5 HERC2 CRYAA
4 diabetes insipidus 31.8 WFS1 CRH CISD2 AVP
5 deafness, autosomal dominant 6 30.7 WFS1 CISD2
6 bipolar disorder 30.5 WFS1 TH NCS1 DRD5 CRH
7 optic nerve disease 30.4 WFS1 CRYAA CISD2
8 wolfram syndrome, mitochondrial form 11.4
9 autosomal dominant wolfram syndrome 11.4
10 wfs1 wolfram syndrome spectrum disorder 11.2
11 mohr-tranebjaerg syndrome 11.0
12 diabetes and deafness, maternally inherited 11.0
13 3-methylglutaconic aciduria, type iii 11.0
14 waterhouse-friderichsen syndrome 10.9
15 branchiootic syndrome 1 10.9
16 autosomal recessive disease 10.6
17 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.5
18 sensorineural hearing loss 10.5
19 diabetes mellitus 10.5
20 microvascular complications of diabetes 5 10.4
21 rare genetic deafness 10.4
22 pituitary infarct 10.4 CRH AVP
23 epiphyseal dysplasia, multiple, with early-onset diabetes mellitus 10.4 WFS1 HSPA5 ATF6
24 anterior cerebral artery infarction 10.4 TH AVP
25 binswanger's disease 10.4 RECK CRH
26 sheehan syndrome 10.4 CRH AVP
27 marden-walker syndrome 10.4 WFS1 EFEMP1
28 hypothalamic disease 10.3 CRH AVP
29 gangliocytoma 10.3 TH CRH
30 substance dependence 10.3 DRD5 CRH AVP
31 prion disease 10.3 TH HSPA5 ATF6
32 ataxia and polyneuropathy, adult-onset 10.3
33 neuropathy 10.3
34 yemenite deaf-blind hypopigmentation syndrome 10.3
35 hypogonadism 10.3
36 pathologic nystagmus 10.3
37 adjustment disorder 10.3 TH CRH
38 type 1 diabetes mellitus 10.2
39 specific developmental disorder 10.2 TH DRD5 CRYAA CRH
40 inappropriate adh syndrome 10.2 CRH AVP
41 neurogenic bladder 10.2
42 hydronephrosis 10.2
43 insulinoma 10.2
44 hereditary optic neuropathy 10.2
45 major affective disorder 8 10.1
46 major affective disorder 9 10.1
47 mood disorder 10.1
48 peripheral nervous system disease 10.1
49 peptic ulcer disease 10.1
50 rare neurodegenerative disease 10.1

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



Diseases related to Wolfram Syndrome

Symptoms & Phenotypes for Wolfram Syndrome

Human phenotypes related to Wolfram Syndrome:

58 31 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 diabetes mellitus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000819
2 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
3 optic atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000648
4 polydipsia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001959
5 diabetes insipidus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000873
6 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
7 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
8 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
9 feeding difficulties in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0008872
10 nephropathy 58 31 frequent (33%) Frequent (79-30%) HP:0000112
11 recurrent urinary tract infections 58 31 frequent (33%) Frequent (79-30%) HP:0000010
12 dysuria 58 31 frequent (33%) Frequent (79-30%) HP:0100518
13 abnormality of mesentery morphology 58 31 frequent (33%) Frequent (79-30%) HP:0100016
14 seizure 31 frequent (33%) HP:0001250
15 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
16 sleep disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0002360
17 constipation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002019
18 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
19 developmental regression 58 31 occasional (7.5%) Occasional (29-5%) HP:0002376
20 hallucinations 58 31 occasional (7.5%) Occasional (29-5%) HP:0000738
21 joint stiffness 58 31 occasional (7.5%) Occasional (29-5%) HP:0001387
22 malabsorption 58 31 occasional (7.5%) Occasional (29-5%) HP:0002024
23 delayed puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000823
24 myopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003198
25 anemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001903
26 ophthalmoplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000602
27 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
28 glaucoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0000501
29 gastrointestinal hemorrhage 58 31 occasional (7.5%) Occasional (29-5%) HP:0002239
30 peripheral neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0009830
31 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
32 gastric ulcer 58 31 occasional (7.5%) Occasional (29-5%) HP:0002592
33 dementia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000726
34 male hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000026
35 central apnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002871
36 abnormal autonomic nervous system physiology 31 occasional (7.5%) HP:0012332
37 seizures 58 Frequent (79-30%)
38 dysautonomia 58 Occasional (29-5%)
39 behavioral abnormality 58 Occasional (29-5%)
40 abnormality of the urinary system 58 Frequent (79-30%)
41 hypogonadism 58 Occasional (29-5%)

UMLS symptoms related to Wolfram Syndrome:


seizures; ataxia; tremor

MGI Mouse Phenotypes related to Wolfram Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.18 AVP BAMBI CISD2 CRH DRD5 EFEMP1
2 endocrine/exocrine gland MP:0005379 10.11 ATF6 BAMBI CISD2 CRH DRD5 EFEMP1
3 integument MP:0010771 10.06 BAMBI CISD2 CRH EFEMP1 HSPA5 PCSK2
4 mortality/aging MP:0010768 10 ATF6 AVP CISD2 DRD5 EFEMP1 HERC2
5 liver/biliary system MP:0005370 9.8 ATF6 BAMBI CRH EFEMP1 RECK SCG5
6 normal MP:0002873 9.56 AVP BAMBI CRH DRD5 EFEMP1 HSPA5
7 renal/urinary system MP:0005367 9.23 AVP CISD2 CRH DRD5 EFEMP1 HSPA5

Drugs & Therapeutics for Wolfram Syndrome

Drugs for Wolfram Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 36)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcysteine Approved, Investigational Phase 2, Phase 3 616-91-1 12035
2
Metformin Approved Phase 2, Phase 3 657-24-9 4091 14219
3
Iron Approved Phase 2, Phase 3 7439-89-6 23925 29936
4
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
5 Antidotes Phase 2, Phase 3
6 Chelating Agents Phase 2, Phase 3
7 Respiratory System Agents Phase 2, Phase 3
8 Protective Agents Phase 2, Phase 3
9 Hormone Antagonists Phase 2, Phase 3
10 Incretins Phase 2, Phase 3
11 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
12 Hormones Phase 2, Phase 3
13 Sitagliptin Phosphate Phase 2, Phase 3
14 Expectorants Phase 2, Phase 3
15 Iron Chelating Agents Phase 2, Phase 3
16 Antioxidants Phase 2, Phase 3
17
protease inhibitors Phase 2, Phase 3
18 Hypoglycemic Agents Phase 2, Phase 3
19 Antiviral Agents Phase 2, Phase 3
20 HIV Protease Inhibitors Phase 2, Phase 3
21 Anti-Infective Agents Phase 2, Phase 3
22 N-monoacetylcystine Phase 2, Phase 3
23
Valproic acid Approved, Investigational Phase 2 99-66-1 3121
24
Dantrolene Approved, Investigational Phase 1, Phase 2 7261-97-4 2952 6914273
25 Psychotropic Drugs Phase 2
26 Neurotransmitter Agents Phase 2
27 Anticonvulsants Phase 2
28
Exenatide Approved, Investigational 141758-74-9 15991534
29 Glucagon-Like Peptide 1
30 Anti-Obesity Agents
31 insulin
32 Insulin, Globin Zinc
33 Arginine Vasopressin
34 Immunoglobulins
35 Antibodies
36 Autoantibodies

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy Unknown status NCT02882477 Phase 2, Phase 3 Deferiprone;Acetylcysteine;Sitagliptin and Metformin
2 A Pivotal, International, Randomised, Double-blind, Efficacy and Safety Trial of Sodium Valproate, in Paediatric and Adult Patients With Wolfram Syndrome Recruiting NCT03717909 Phase 2 Sodium Valproate 200Mg E/C Tablet;Sodium Valproate matched placebo
3 A Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome Active, not recruiting NCT02829268 Phase 1, Phase 2 dantrolene sodium
4 GLP Analogs for Diabetes in Wolfram Syndrome Patients Unknown status NCT01302327 Exenatide
5 Tracking Neurodegeneration in Early Wolfram Syndrome Completed NCT02455414
6 International Tracking Neurodegeneration in Early Wolfram Syndrome Recruiting NCT03951298
7 Wolfram Syndrome International Registry and Clinical Study Recruiting NCT02841553
8 Accurate Diagnosis of Diabetes for Appropriate Management Recruiting NCT03988764

Search NIH Clinical Center for Wolfram Syndrome

Cochrane evidence based reviews: wolfram syndrome

Genetic Tests for Wolfram Syndrome

Genetic tests related to Wolfram Syndrome:

# Genetic test Affiliating Genes
1 Wolfram Syndrome 29

Anatomical Context for Wolfram Syndrome

MalaCards organs/tissues related to Wolfram Syndrome:

40
Eye, Pituitary, Brain, Skeletal Muscle, Pancreas, Hypothalamus, Bone

Publications for Wolfram Syndrome

Articles related to Wolfram Syndrome:

(show top 50) (show all 630)
# Title Authors PMID Year
1
Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome. 61 6 54
19042979 2009
2
WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon. 6 54 61
18806274 2008
3
Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations. 61 54 6
18040659 2008
4
Common variants in WFS1 confer risk of type 2 diabetes. 6 54 61
17603484 2007
5
Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families. 6 54 61
15151504 2004
6
Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay. 61 6 54
12754709 2003
7
Identification of novel WFS1 mutations in Italian children with Wolfram syndrome. 61 54 6
11295831 2001
8
Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees. 61 54 6
11161832 2001
9
Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q. 6 61 54
10739754 2000
10
Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. 61 54 6
10521293 1999
11
Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. 6 54 61
9817917 1998
12
A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). 61 54 6
9771706 1998
13
A donor splice site mutation in CISD2 generates multiple truncated, non-functional isoforms in Wolfram syndrome type 2 patients. 6 61
29237418 2017
14
Phenotype Prediction of Pathogenic Nonsynonymous Single Nucleotide Polymorphisms in WFS1. 61 6
26435059 2015
15
Selective cognitive and psychiatric manifestations in Wolfram Syndrome. 6 61
26025012 2015
16
Wolfram syndrome 2: a novel CISD2 mutation identified in Italian siblings. 6 61
25371195 2015
17
A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2. 6 61
25056293 2014
18
Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. 6 61
25211237 2014
19
Phenotypic characteristics of early Wolfram syndrome. 61 6
23981289 2013
20
Wolfram syndrome: new mutations, different phenotype. 6 61
22238590 2012
21
Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment. 61 6
21538838 2011
22
Congenital cataracts in two siblings with Wolfram syndrome. 6 61
21067485 2010
23
A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. 6 61
17846994 2007
24
Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. 6 61
11260218 2001
25
Evidence of an increased risk of hearing loss in heterozygous carriers in a Wolfram syndrome family. 6 61
9856492 1998
26
Natural history and clinical characteristics of 50 patients with Wolfram syndrome. 20 61
29728875 2018
27
Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease. 20 61
29774890 2018
28
Molecular diagnostic experience of whole-exome sequencing in adult patients. 6
26633545 2016
29
Lamination of the Outer Plexiform Layer in Optic Atrophy Caused by Dominant WFS1 Mutations. 6
26875006 2016
30
Expression of the diabetes risk gene wolframin (WFS1) in the human retina. 61 54
19523951 2009
31
Wolfram syndrome 1 (Wfs1) mRNA expression in the normal mouse brain during postnatal development. 61 54
19428703 2009
32
The novel compound heterozygous mutations, V434del and W666X, in WFS1 gene causing the Wolfram syndrome in a Chinese family. 61 54
19160074 2009
33
Association study of the effect of WFS1 polymorphisms on risk of type 2 diabetes in Japanese population. 54 61
19258739 2008
34
In search of the DFNA11 myosin VIIA low- and mid-frequency auditory genetic modifier. 61 54
18667942 2008
35
Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1. 61 54
18688868 2008
36
Distribution of Wfs1 protein in the central nervous system of the mouse and its relation to clinical symptoms of the Wolfram syndrome. 54 61
18551525 2008
37
Hearing impairment in genotyped Wolfram syndrome patients. 54 61
18700423 2008
38
Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program. 54 61
18060660 2008
39
Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress. 54 61
17947299 2008
40
Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf-Hirschhorn syndrome. 61 54
17637805 2007
41
The wolframin His611Arg polymorphism influences medication overuse headache. 61 54
17719176 2007
42
Identification of novel mutations in WFS1 and genotype-phenotype correlation in Wolfram syndrome. 61 54
17568405 2007
43
A novel mutation in the WFS1 gene identified in a Taiwanese family with low-frequency hearing impairment. 54 61
17517145 2007
44
A new mutation in WFS1 gene (C.1522-1523delTA, Y508fsX421) may be responsible for early appearance of clinical features of Wolfram syndrome and suicidal behaviour. 61 54
17187023 2006
45
[Wolfram syndrome: from definition to molecular bases]. 54 61
17160206 2006
46
WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic reticulum. 54 61
16989814 2006
47
A novel mutation of WFS1 gene in a Japanese man of Wolfram syndrome with positive diabetes-related antibodies. 61 54
16442662 2006
48
Wolfram syndrome-associated mutations lead to instability and proteasomal degradation of wolframin. 61 54
16806192 2006
49
Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. 61 54
16648378 2006
50
Genetics of hearing loss: Allelism and modifier genes produce a phenotypic continuum. 61 54
16550584 2006

Variations for Wolfram Syndrome

ClinVar genetic disease variations for Wolfram Syndrome:

6 (show top 50) (show all 71)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 WFS1 WFS1, 2-BP DEL, 2812TC Deletion Pathogenic 4507 GRCh37:
GRCh38:
2 WFS1 WFS1, 15-BP DEL, NT1685 Deletion Pathogenic 4508 GRCh37:
GRCh38:
3 WFS1 NM_006005.3(WFS1):c.2171C>T (p.Pro724Leu) SNV Pathogenic 4509 rs28937890 GRCh37: 4:6303693-6303693
GRCh38: 4:6301966-6301966
4 WFS1 NM_006005.3(WFS1):c.2084G>T (p.Gly695Val) SNV Pathogenic 4510 rs28937891 GRCh37: 4:6303606-6303606
GRCh38: 4:6301879-6301879
5 WFS1 NM_006005.3(WFS1):c.1944G>A (p.Trp648Ter) SNV Pathogenic 4511 rs104893879 GRCh37: 4:6303466-6303466
GRCh38: 4:6301739-6301739
6 WFS1 NM_006005.3(WFS1):c.1511C>T (p.Pro504Leu) SNV Pathogenic 4512 rs28937892 GRCh37: 4:6303033-6303033
GRCh38: 4:6301306-6301306
7 WFS1 WFS1, 7-BP INS, NT1610 Insertion Pathogenic 4513 GRCh37:
GRCh38:
8 WFS1 NM_006005.3(WFS1):c.1385_1393del (p.Glu462_Thr464del) Deletion Pathogenic 4514 rs1578609780 GRCh37: 4:6302902-6302910
GRCh38: 4:6301175-6301183
9 WFS1 NM_006005.3(WFS1):c.460+1G>A SNV Pathogenic 4515 rs1191510461 GRCh37: 4:6290859-6290859
GRCh38: 4:6289132-6289132
10 WFS1 NM_006005.3(WFS1):c.676C>T (p.Gln226Ter) SNV Pathogenic 4516 rs104893880 GRCh37: 4:6293688-6293688
GRCh38: 4:6291961-6291961
11 WFS1 NM_006005.3(WFS1):c.2455C>T (p.Gln819Ter) SNV Pathogenic 4517 rs104893881 GRCh37: 4:6303977-6303977
GRCh38: 4:6302250-6302250
12 WFS1 NM_006005.3(WFS1):c.409_424dup (p.Val142fs) Duplication Pathogenic 4519 rs1362648752 GRCh37: 4:6290805-6290806
GRCh38: 4:6289078-6289079
13 WFS1 WFS1, 16-BP DEL, NT1362 Deletion Pathogenic 4525 GRCh37:
GRCh38:
14 WFS1 NM_006005.3(WFS1):c.2119G>T (p.Val707Phe) SNV Pathogenic 30552 rs71524377 GRCh37: 4:6303641-6303641
GRCh38: 4:6301914-6301914
15 WFS1 WFS1, 8-BP DEL, NT2106 Deletion Pathogenic 30553 GRCh37:
GRCh38:
16 WFS1 NM_006005.3(WFS1):c.2051C>T (p.Ala684Val) SNV Pathogenic 30556 rs387906930 GRCh37: 4:6303573-6303573
GRCh38: 4:6301846-6301846
17 WFS1 V415del Deletion Pathogenic 30557 GRCh37:
GRCh38:
18 WFS1 WFS1, 4-BP DEL, 1387CTCT Deletion Pathogenic 30558 GRCh37:
GRCh38:
19 WFS1 NM_006005.3(WFS1):c.124C>T (p.Arg42Ter) SNV Pathogenic 189251 rs71530923 GRCh37: 4:6279306-6279306
GRCh38: 4:6277579-6277579
20 CISD2 , SLC9B1 NM_001008388.5(CISD2):c.109G>C (p.Glu37Gln) SNV Pathogenic 892 rs63749888 GRCh37: 4:103806378-103806378
GRCh38: 4:102885221-102885221
21 CISD2 , SLC9B1 NM_001008388.4(CISD2):c.(104_304)-84_318+724del Deletion Pathogenic 156218 GRCh37:
GRCh38: 4:102885132-102887186
22 CISD2 NM_001008388.5(CISD2):c.103+1G>A SNV Pathogenic 638297 rs1578307302 GRCh37: 4:103790345-103790345
GRCh38: 4:102869188-102869188
23 WFS1 NM_006005.3(WFS1):c.873C>G (p.Tyr291Ter) SNV Pathogenic 212616 rs777580652 GRCh37: 4:6302395-6302395
GRCh38: 4:6300668-6300668
24 WFS1 NM_006005.3(WFS1):c.2369C>A (p.Ser790Ter) SNV Pathogenic 212614 rs369107336 GRCh37: 4:6303891-6303891
GRCh38: 4:6302164-6302164
25 WFS1 NM_006005.3(WFS1):c.439del (p.Arg147fs) Deletion Pathogenic 620589 rs1560408865 GRCh37: 4:6290836-6290836
GRCh38: 4:6289109-6289109
26 WFS1 NM_006005.3(WFS1):c.409_424dup (p.Val142fs) Duplication Pathogenic 4519 rs1362648752 GRCh37: 4:6290805-6290806
GRCh38: 4:6289078-6289079
27 WFS1 NM_006005.3(WFS1):c.2051C>T (p.Ala684Val) SNV Pathogenic 30556 rs387906930 GRCh37: 4:6303573-6303573
GRCh38: 4:6301846-6301846
28 WFS1 NM_006005.3(WFS1):c.2224dup (p.Cys742fs) Duplication Pathogenic 807719 rs1578612324 GRCh37: 4:6303745-6303746
GRCh38: 4:6302018-6302019
29 WFS1 NM_006005.3(WFS1):c.2638_2643del (p.Asp880_Phe881del) Deletion Pathogenic 807720 rs1272826809 GRCh37: 4:6304156-6304161
GRCh38: 4:6302429-6302434
30 WFS1 NM_006005.3(WFS1):c.1620G>A (p.Trp540Ter) SNV Pathogenic 929945 GRCh37: 4:6303142-6303142
GRCh38: 4:6301415-6301415
31 WFS1 NM_006005.3(WFS1):c.1949_1950del (p.Tyr650fs) Deletion Pathogenic 929946 GRCh37: 4:6303470-6303471
GRCh38: 4:6301743-6301744
32 WFS1 NM_001145853.1(WFS1):c.2648_2651del (p.Phe883fs) Deletion Pathogenic 209207 rs797045076 GRCh37: 4:6304168-6304171
GRCh38: 4:6302441-6302444
33 WFS1 NM_006005.3(WFS1):c.1829del (p.Leu610fs) Deletion Pathogenic 802051 rs1578611240 GRCh37: 4:6303350-6303350
GRCh38: 4:6301623-6301623
34 WFS1 NM_006005.3(WFS1):c.2007T>G (p.Tyr669Ter) SNV Pathogenic 802052 rs1443751733 GRCh37: 4:6303529-6303529
GRCh38: 4:6301802-6301802
35 WFS1 NM_006005.3(WFS1):c.2663C>A (p.Ser888Ter) SNV Pathogenic 1031591 GRCh37: 4:6304185-6304185
GRCh38: 4:6302458-6302458
36 WFS1 NM_006005.3(WFS1):c.1610G>A (p.Cys537Tyr) SNV Likely pathogenic 215390 rs199910987 GRCh37: 4:6303132-6303132
GRCh38: 4:6301405-6301405
37 WFS1 NM_006005.3(WFS1):c.320G>A (p.Gly107Glu) SNV Likely pathogenic 982858 GRCh37: 4:6290718-6290718
GRCh38: 4:6288991-6288991
38 WFS1 NM_006005.3(WFS1):c.578dup (p.Gln194fs) Duplication Likely pathogenic 996897 GRCh37: 4:6293039-6293040
GRCh38: 4:6291312-6291313
39 WFS1 NM_006005.3(WFS1):c.568_570AAG[3] (p.Lys193del) Microsatellite Likely pathogenic 623222 rs752461187 GRCh37: 4:6293031-6293033
GRCh38: 4:6291304-6291306
40 WFS1 NM_006005.3(WFS1):c.1237_1239TTC[1] (p.Phe414del) Microsatellite Likely pathogenic 212611 rs797046112 GRCh37: 4:6302757-6302759
GRCh38: 4:6301030-6301032
41 WFS1 NM_006005.3(WFS1):c.1692_1697CCTCTT[1] (p.565_566LF[1]) Microsatellite Likely pathogenic 212612 rs797046113 GRCh37: 4:6303211-6303216
GRCh38: 4:6301484-6301489
42 WFS1 NM_006005.3(WFS1):c.1672C>T (p.Arg558Cys) SNV Likely pathogenic 198835 rs199946797 GRCh37: 4:6303194-6303194
GRCh38: 4:6301467-6301467
43 WFS1 NM_006005.3(WFS1):c.2654C>T (p.Pro885Leu) SNV Likely pathogenic 437297 rs372855769 GRCh37: 4:6304176-6304176
GRCh38: 4:6302449-6302449
44 WFS1 NM_006005.3(WFS1):c.2263T>C (p.Cys755Arg) SNV Likely pathogenic 209206 rs797045075 GRCh37: 4:6303785-6303785
GRCh38: 4:6302058-6302058
45 WFS1 NM_006005.3(WFS1):c.2209G>A (p.Glu737Lys) SNV Conflicting interpretations of pathogenicity 143132 rs147834269 GRCh37: 4:6303731-6303731
GRCh38: 4:6302004-6302004
46 WFS1 NM_006005.3(WFS1):c.1957C>T (p.Arg653Cys) SNV Uncertain significance 178597 rs201064551 GRCh37: 4:6303479-6303479
GRCh38: 4:6301752-6301752
47 WFS1 NM_006005.3(WFS1):c.1235T>C (p.Val412Ala) SNV Uncertain significance 215387 rs144951440 GRCh37: 4:6302757-6302757
GRCh38: 4:6301030-6301030
48 WFS1 NM_006005.3(WFS1):c.2029G>A (p.Ala677Thr) SNV Uncertain significance 198834 rs757027394 GRCh37: 4:6303551-6303551
GRCh38: 4:6301824-6301824
49 WFS1 NM_006005.3(WFS1):c.683G>A (p.Arg228His) SNV Uncertain significance 198190 rs150771247 GRCh37: 4:6293695-6293695
GRCh38: 4:6291968-6291968
50 WFS1 NM_006005.3(WFS1):c.1167T>G (p.Asp389Glu) SNV Uncertain significance 215385 rs201282601 GRCh37: 4:6302689-6302689
GRCh38: 4:6300962-6300962

Expression for Wolfram Syndrome

Search GEO for disease gene expression data for Wolfram Syndrome.

Pathways for Wolfram Syndrome

Pathways related to Wolfram Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Protein processing in endoplasmic reticulum hsa04141

GO Terms for Wolfram Syndrome

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

# Name GO ID Score Top Affiliating Genes
1 intracellular membrane-bounded organelle GO:0043231 9.8 PCSK2 NCS1 HSPA5 CISD3 CISD2 CISD1
2 dendrite GO:0030425 9.55 WFS1 TH PCSK2 NCS1 AVP
3 secretory granule GO:0030141 9.43 SCG5 PCSK2 AVP
4 integral component of endoplasmic reticulum membrane GO:0030176 9.26 WFS1 SYVN1 HSPA5 ATF6
5 smooth endoplasmic reticulum GO:0005790 8.8 TH SYVN1 HSPA5

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

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 response to ethanol GO:0045471 9.74 TH CRH AVP
2 ubiquitin-dependent ERAD pathway GO:0030433 9.65 WFS1 SYVN1 HSPA5
3 response to immobilization stress GO:0035902 9.58 TH CRH
4 protein refolding GO:0042026 9.58 HSPA5 CRYAA
5 peptide hormone processing GO:0016486 9.56 SCG5 PCSK2
6 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 9.55 WFS1 SYVN1
7 response to corticosterone GO:0051412 9.54 TH CRH
8 IRE1-mediated unfolded protein response GO:0036498 9.54 WFS1 SYVN1 HSPA5
9 multicellular organism aging GO:0010259 9.52 TH CISD2
10 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress GO:1990440 9.51 HSPA5 ATF6
11 endoplasmic reticulum unfolded protein response GO:0030968 9.5 WFS1 HSPA5 ATF6
12 ER overload response GO:0006983 9.49 WFS1 HSPA5
13 cellular response to manganese ion GO:0071287 9.46 TH HSPA5
14 ATF6-mediated unfolded protein response GO:0036500 9.43 HSPA5 ATF6
15 response to cocaine GO:0042220 9.43 HSPA5 DRD5 CRH
16 mating behavior GO:0007617 9.4 TH DRD5
17 visual perception GO:0007601 9.35 WFS1 TH EFEMP1 CRYAA ATF6
18 response to ether GO:0045472 9.16 TH CRH
19 synaptic transmission, dopaminergic GO:0001963 8.8 TH DRD5 CRH

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

# Name GO ID Score Top Affiliating Genes
1 ubiquitin protein ligase binding GO:0031625 9.62 WFS1 HSPA5 HERC2 ATF6
2 iron-sulfur cluster binding GO:0051536 9.43 CISD3 CISD2 CISD1
3 unfolded protein binding GO:0051082 9.26 SYVN1 SCG5 HSPA5 CRYAA
4 dopamine binding GO:0035240 9.16 TH DRD5
5 2 iron, 2 sulfur cluster binding GO:0051537 8.8 CISD3 CISD2 CISD1

Sources for Wolfram Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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