WFS
MCID: WLF004
MIFTS: 60

Wolfram Syndrome (WFS)

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

Aliases & Classifications for Wolfram Syndrome

MalaCards integrated aliases for Wolfram Syndrome:

Name: Wolfram Syndrome 12 74 52 25 58 36 29 54 6 43 15 39 71
Didmoad Syndrome 52 25 58
Diabetes Insipidus and Mellitus with Optic Atrophy and Deafness 52 25
Didmoad 52 25
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 25
Didmoadud 25
Wfs 52

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

Genetics Home Reference : 25 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 syndrome 1, 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 Neuroscience. The drugs Acetylcysteine and Iron have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and kidney, and related phenotypes are sensorineural hearing impairment and optic atrophy

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

NIH Rare Diseases : 52 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 : 74 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 217)
# Related Disease Score Top Affiliating Genes
1 wolfram syndrome 2 34.5 WFS1 SLC9B1 CISD3 CISD2 CISD1
2 wolfram syndrome 1 33.3 WFS1 SYVN1 INS HSPA5 CRYAA CRH
3 3-methylglutaconic aciduria, type iii 31.8 WFS1 CRYAA CISD2 BAMBI
4 diabetes insipidus 31.7 WFS1 INS CRH CISD2 AVP
5 deafness, autosomal dominant 6 31.2 WFS1 CISD2
6 optic nerve disease 30.7 WFS1 CRYAA CISD2
7 insulinoma 30.6 WFS1 PCSK2 INS
8 secondary adrenal insufficiency 30.4 INS AVP
9 pituitary gland disease 30.2 INS CRH AVP
10 wolfram syndrome, mitochondrial form 12.6
11 autosomal dominant wolfram syndrome 12.5
12 wfs1 wolfram syndrome spectrum disorder 12.4
13 wolfram-like syndrome, autosomal dominant 12.0
14 waterhouse-friderichsen syndrome 11.3
15 mohr-tranebjaerg syndrome 11.2
16 diabetes and deafness, maternally inherited 11.2
17 branchiootic syndrome 1 10.9
18 autosomal recessive disease 10.7
19 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.6
20 sensorineural hearing loss 10.6
21 marden-walker syndrome 10.5 WFS1 EFEMP1
22 binswanger's disease 10.5 RECK CRH
23 microvascular complications of diabetes 5 10.5
24 diabetes mellitus 10.4
25 ataxia and polyneuropathy, adult-onset 10.4
26 inappropriate adh syndrome 10.4 CRH AVP
27 early-onset nuclear cataract 10.4 WFS1 CRYAA
28 epiphyseal dysplasia, multiple, with early-onset diabetes mellitus 10.4 WFS1 INS ATF6
29 hyperproinsulinemia 10.4 PCSK2 INS
30 colorectal cancer 10.4
31 pituitary tumors 10.4
32 hypogonadism 10.3
33 neuropathy 10.3
34 substance dependence 10.3 DRD5 CRH AVP
35 pituitary infarct 10.3 INS CRH AVP
36 hypothalamic disease 10.3 INS CRH AVP
37 sheehan syndrome 10.3 INS CRH AVP
38 adrenal cortical hypofunction 10.3 INS CRH AVP
39 pathologic nystagmus 10.3
40 adenocarcinoma 10.3
41 tubular adenocarcinoma 10.3
42 adrenal gland disease 10.3 INS CRH AVP
43 yemenite deaf-blind hypopigmentation syndrome 10.3
44 pituitary apoplexy 10.3 INS AVP
45 substance abuse 10.3 INS DRD5 CRH
46 diabetes mellitus, type i 10.2
47 mucormycosis 10.2 INS HSPA5
48 autoimmune disease 10.2
49 allergic hypersensitivity disease 10.2
50 amelanotic melanoma 10.2

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 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
2 optic atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000648
3 polydipsia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001959
4 diabetes insipidus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000873
5 diabetes mellitus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000819
6 feeding difficulties in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0008872
7 nephropathy 58 31 frequent (33%) Frequent (79-30%) HP:0000112
8 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
9 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
10 recurrent urinary tract infections 58 31 frequent (33%) Frequent (79-30%) HP:0000010
11 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
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 hallucinations 58 31 occasional (7.5%) Occasional (29-5%) HP:0000738
17 joint stiffness 58 31 occasional (7.5%) Occasional (29-5%) HP:0001387
18 malabsorption 58 31 occasional (7.5%) Occasional (29-5%) HP:0002024
19 sleep disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0002360
20 developmental regression 58 31 occasional (7.5%) Occasional (29-5%) HP:0002376
21 delayed puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000823
22 myopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003198
23 peripheral neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0009830
24 anemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001903
25 gastrointestinal hemorrhage 58 31 occasional (7.5%) Occasional (29-5%) HP:0002239
26 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
27 ophthalmoplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000602
28 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
29 glaucoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0000501
30 constipation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002019
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 behavioral abnormality 58 Occasional (29-5%)
38 seizures 58 Frequent (79-30%)
39 abnormality of the urinary system 58 Frequent (79-30%)
40 hypogonadism 58 Occasional (29-5%)
41 dysautonomia 58 Occasional (29-5%)

UMLS symptoms related to Wolfram Syndrome:


seizures, ataxia, tremor

MGI Mouse Phenotypes related to Wolfram Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.14 AVP BAMBI CDKAL1 CISD2 CRH DRD5
2 endocrine/exocrine gland MP:0005379 10.11 ATF6 BAMBI CDKAL1 CISD2 CRH DRD5
3 integument MP:0010771 10.06 BAMBI CDKAL1 CISD2 CRH EFEMP1 HSPA5
4 adipose tissue MP:0005375 9.98 CDKAL1 CISD2 CRH EFEMP1 HSPA5 INS
5 mortality/aging MP:0010768 9.97 ATF6 AVP CISD2 DRD5 EFEMP1 HSPA5
6 liver/biliary system MP:0005370 9.86 ATF6 BAMBI CDKAL1 CRH EFEMP1 INS
7 normal MP:0002873 9.61 AVP BAMBI CDKAL1 CRH DRD5 EFEMP1
8 renal/urinary system MP:0005367 9.28 AVP BAMBI CISD2 CRH DRD5 EFEMP1

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
Iron Approved, Experimental Phase 2, Phase 3 15438-31-0, 7439-89-6 27284 23925
3
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
4
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
5 Hormones Phase 2, Phase 3
6 Hypoglycemic Agents Phase 2, Phase 3
7 Hormone Antagonists Phase 2, Phase 3
8 Incretins Phase 2, Phase 3
9 Respiratory System Agents Phase 2, Phase 3
10 Antidotes Phase 2, Phase 3
11 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
12 Antioxidants Phase 2, Phase 3
13 Chelating Agents Phase 2, Phase 3
14 Anti-Infective Agents Phase 2, Phase 3
15
protease inhibitors Phase 2, Phase 3
16 Antiviral Agents Phase 2, Phase 3
17 Iron Chelating Agents Phase 2, Phase 3
18 HIV Protease Inhibitors Phase 2, Phase 3
19 Sitagliptin Phosphate Phase 2, Phase 3
20 Protective Agents Phase 2, Phase 3
21 Expectorants Phase 2, Phase 3
22 N-monoacetylcystine Phase 2, Phase 3
23
Dantrolene Approved, Investigational Phase 1, Phase 2 7261-97-4 6914273 2952
24
Valproic acid Approved, Investigational Phase 2 99-66-1 3121
25 Psychotropic Drugs Phase 2
26 Anticonvulsants Phase 2
27 Neurotransmitter Agents Phase 2
28
Exenatide Approved, Investigational 141758-74-9 15991534
29 Anti-Obesity Agents
30 Glucagon-Like Peptide 1
31 Insulin, Globin Zinc
32 insulin
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 Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome Recruiting NCT02829268 Phase 1, Phase 2 dantrolene sodium
3 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
4 GLP Analogs for Diabetes in Wolfram Syndrome Patients Unknown status NCT01302327 Exenatide
5 Tracking Neurodegeneration in Early Wolfram Syndrome Completed NCT02455414
6 Wolfram Syndrome International Registry and Clinical Study Recruiting NCT02841553
7 International Tracking Neurodegeneration in Early Wolfram Syndrome Recruiting NCT03951298
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
Brain, Eye, Kidney, Pituitary, Skeletal Muscle, Pancreas, Testes

Publications for Wolfram Syndrome

Articles related to Wolfram Syndrome:

(show top 50) (show all 599)
# Title Authors PMID Year
1
WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon. 54 6 61
18806274 2008
2
Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families. 61 6 54
15151504 2004
3
Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay. 6 61 54
12754709 2003
4
Identification of novel WFS1 mutations in Italian children with Wolfram syndrome. 61 54 6
11295831 2001
5
Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees. 6 61 54
11161832 2001
6
Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q. 61 54 6
10739754 2000
7
Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. 6 61 54
10521293 1999
8
Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. 61 54 6
9817917 1998
9
A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). 6 61 54
9771706 1998
10
A donor splice site mutation in CISD2 generates multiple truncated, non-functional isoforms in Wolfram syndrome type 2 patients. 61 6
29237418 2017
11
Wolfram syndrome 2: a novel CISD2 mutation identified in Italian siblings. 6 61
25371195 2015
12
A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2. 6 61
25056293 2014
13
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
14
WFS1 Wolfram Syndrome Spectrum Disorder 6 61
20301750 2009
15
A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. 6 61
17846994 2007
16
Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. 61 6
11260218 2001
17
Natural history and clinical characteristics of 50 patients with Wolfram syndrome. 61 52
29728875 2018
18
Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease. 61 52
29774890 2018
19
Expression of the diabetes risk gene wolframin (WFS1) in the human retina. 54 61
19523951 2009
20
Wolfram syndrome 1 (Wfs1) mRNA expression in the normal mouse brain during postnatal development. 54 61
19428703 2009
21
The novel compound heterozygous mutations, V434del and W666X, in WFS1 gene causing the Wolfram syndrome in a Chinese family. 61 54
19160074 2009
22
Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome. 54 61
19042979 2009
23
Association study of the effect of WFS1 polymorphisms on risk of type 2 diabetes in Japanese population. 61 54
19258739 2008
24
In search of the DFNA11 myosin VIIA low- and mid-frequency auditory genetic modifier. 61 54
18667942 2008
25
Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1. 61 54
18688868 2008
26
Distribution of Wfs1 protein in the central nervous system of the mouse and its relation to clinical symptoms of the Wolfram syndrome. 61 54
18551525 2008
27
Hearing impairment in genotyped Wolfram syndrome patients. 54 61
18700423 2008
28
Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program. 61 54
18060660 2008
29
Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations. 61 54
18040659 2008
30
Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress. 54 61
17947299 2008
31
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
32
The wolframin His611Arg polymorphism influences medication overuse headache. 61 54
17719176 2007
33
Common variants in WFS1 confer risk of type 2 diabetes. 61 54
17603484 2007
34
Identification of novel mutations in WFS1 and genotype-phenotype correlation in Wolfram syndrome. 61 54
17568405 2007
35
A novel mutation in the WFS1 gene identified in a Taiwanese family with low-frequency hearing impairment. 54 61
17517145 2007
36
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
37
WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic reticulum. 61 54
16989814 2006
38
[Wolfram syndrome: from definition to molecular bases]. 61 54
17160206 2006
39
A novel mutation of WFS1 gene in a Japanese man of Wolfram syndrome with positive diabetes-related antibodies. 54 61
16442662 2006
40
Wolfram syndrome-associated mutations lead to instability and proteasomal degradation of wolframin. 54 61
16806192 2006
41
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
42
Genetics of hearing loss: Allelism and modifier genes produce a phenotypic continuum. 61 54
16550584 2006
43
Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified. 61 54
16151413 2005
44
WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells. 54 61
16195229 2005
45
A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss. 54 61
16353398 2005
46
[Heterogeneous mutations of Wolfram syndrome I gene responsible for low frequency nonsyndromic hearing loss]. 54 61
16408729 2005
47
[A novel mutation of WFS1 gene in Chinese patients with Wolfram syndrome]. 54 61
16321270 2005
48
Identification of a novel WFS1 mutation (AFF344-345ins) in Japanese patients with Wolfram syndrome. 61 54
16005363 2005
49
Expressional and functional studies of Wolframin, the gene function deficient in Wolfram syndrome, in mice and patient cells. 54 61
16087305 2005
50
Wolframin mutations and hospitalization for psychiatric illness. 61 54
15852062 2005

Variations for Wolfram Syndrome

ClinVar genetic disease variations for Wolfram Syndrome:

6 (show top 50) (show all 59) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 WFS1 NM_006005.3(WFS1):c.1829del (p.Leu610fs)deletion Pathogenic 802051 4:6303350-6303350 4:6301623-6301623
2 WFS1 NM_006005.3(WFS1):c.2007T>G (p.Tyr669Ter)SNV Pathogenic 802052 4:6303529-6303529 4:6301802-6301802
3 WFS1 NM_006005.3(WFS1):c.2224dup (p.Cys742fs)duplication Pathogenic 807719 4:6303745-6303746 4:6302018-6302019
4 WFS1 NM_006005.3(WFS1):c.2638_2643del (p.Asp880_Phe881del)deletion Pathogenic 807720 4:6304156-6304161 4:6302429-6302434
5 WFS1 WFS1, 2-BP DEL, 2812TCdeletion Pathogenic 4507
6 WFS1 WFS1, 15-BP DEL, NT1685deletion Pathogenic 4508
7 WFS1 NM_006005.3(WFS1):c.2084G>T (p.Gly695Val)SNV Pathogenic 4510 rs28937891 4:6303606-6303606 4:6301879-6301879
8 WFS1 NM_006005.3(WFS1):c.1944G>A (p.Trp648Ter)SNV Pathogenic 4511 rs104893879 4:6303466-6303466 4:6301739-6301739
9 WFS1 NM_006005.3(WFS1):c.1511C>T (p.Pro504Leu)SNV Pathogenic 4512 rs28937892 4:6303033-6303033 4:6301306-6301306
10 WFS1 WFS1, 7-BP INS, NT1610insertion Pathogenic 4513
11 WFS1 NM_006005.3(WFS1):c.1385_1393del (p.Glu462_Thr464del)deletion Pathogenic 4514 4:6302902-6302910 4:6301175-6301183
12 WFS1 NM_006005.3(WFS1):c.460+1G>ASNV Pathogenic 4515 4:6290859-6290859 4:6289132-6289132
13 WFS1 NM_006005.3(WFS1):c.676C>T (p.Gln226Ter)SNV Pathogenic 4516 rs104893880 4:6293688-6293688 4:6291961-6291961
14 WFS1 NM_006005.3(WFS1):c.2455C>T (p.Gln819Ter)SNV Pathogenic 4517 rs104893881 4:6303977-6303977 4:6302250-6302250
15 WFS1 NM_006005.3(WFS1):c.409_424dup (p.Val142fs)duplication Pathogenic 4519 rs1362648752 4:6290805-6290806 4:6289078-6289079
16 WFS1 WFS1, 16-BP DEL, NT1362deletion Pathogenic 4525
17 WFS1 NM_006005.3(WFS1):c.2119G>T (p.Val707Phe)SNV Pathogenic 30552 rs71524377 4:6303641-6303641 4:6301914-6301914
18 WFS1 WFS1, 8-BP DEL, NT2106deletion Pathogenic 30553
19 WFS1 NM_006005.3(WFS1):c.2051C>T (p.Ala684Val)SNV Pathogenic 30556 rs387906930 4:6303573-6303573 4:6301846-6301846
20 WFS1 WFS1, 3-BP DEL, VAL415DELdeletion Pathogenic 30557
21 WFS1 WFS1, 4-BP DEL, 1387CTCTdeletion Pathogenic 30558
22 WFS1 NM_006005.3(WFS1):c.439del (p.Arg147fs)deletion Pathogenic 620589 rs1560408865 4:6290836-6290836 4:6289109-6289109
23 WFS1 NM_006005.3(WFS1):c.873C>G (p.Tyr291Ter)SNV Pathogenic 212616 rs777580652 4:6302395-6302395 4:6300668-6300668
24 WFS1 NM_006005.3(WFS1):c.2369C>A (p.Ser790Ter)SNV Pathogenic 212614 rs369107336 4:6303891-6303891 4:6302164-6302164
25 WFS1 NM_001145853.1(WFS1):c.2648_2651del (p.Phe883fs)deletion Pathogenic/Likely pathogenic 209207 rs797045076 4:6304168-6304171 4:6302441-6302444
26 WFS1 NM_006005.3(WFS1):c.124C>T (p.Arg42Ter)SNV Pathogenic/Likely pathogenic 189251 rs71530923 4:6279306-6279306 4:6277579-6277579
27 WFS1 NM_006005.3(WFS1):c.2263T>C (p.Cys755Arg)SNV Likely pathogenic 209206 rs797045075 4:6303785-6303785 4:6302058-6302058
28 WFS1 NM_006005.3(WFS1):c.568_570AAG[3] (p.Lys193del)short repeat Likely pathogenic 623222 rs752461187 4:6293031-6293033 4:6291304-6291306
29 WFS1 NM_006005.3(WFS1):c.2654C>T (p.Pro885Leu)SNV Likely pathogenic 437297 rs372855769 4:6304176-6304176 4:6302449-6302449
30 WFS1 NM_006005.3(WFS1):c.1237_1239TTC[1] (p.Phe414del)short repeat Likely pathogenic 212611 rs797046112 4:6302757-6302759 4:6301030-6301032
31 WFS1 NM_006005.3(WFS1):c.1692_1697CCTCTT[1] (p.565_566LF[1])short repeat Likely pathogenic 212612 rs797046113 4:6303211-6303216 4:6301484-6301489
32 WFS1 NM_006005.3(WFS1):c.1235T>C (p.Val412Ala)SNV Conflicting interpretations of pathogenicity 215387 rs144951440 4:6302757-6302757 4:6301030-6301030
33 WFS1 NM_006005.3(WFS1):c.1371G>T (p.Arg457Ser)SNV Conflicting interpretations of pathogenicity 215389 rs113446173 4:6302893-6302893 4:6301166-6301166
34 WFS1 NM_006005.3(WFS1):c.1610G>A (p.Cys537Tyr)SNV Conflicting interpretations of pathogenicity 215390 rs199910987 4:6303132-6303132 4:6301405-6301405
35 WFS1 NM_006005.3(WFS1):c.2452C>T (p.Arg818Cys)SNV Conflicting interpretations of pathogenicity 130748 rs35932623 4:6303974-6303974 4:6302247-6302247
36 WFS1 NM_006005.3(WFS1):c.1672C>T (p.Arg558Cys)SNV Conflicting interpretations of pathogenicity 198835 rs199946797 4:6303194-6303194 4:6301467-6301467
37 WFS1 NM_006005.3(WFS1):c.683G>A (p.Arg228His)SNV Conflicting interpretations of pathogenicity 198190 rs150771247 4:6293695-6293695 4:6291968-6291968
38 WFS1 NM_006005.3(WFS1):c.1294C>G (p.Leu432Val)SNV Conflicting interpretations of pathogenicity 137913 rs35031397 4:6302816-6302816 4:6301089-6301089
39 WFS1 NM_006005.3(WFS1):c.2209G>A (p.Glu737Lys)SNV Conflicting interpretations of pathogenicity 143132 rs147834269 4:6303731-6303731 4:6302004-6302004
40 WFS1 NM_006005.3(WFS1):c.716A>G (p.Lys239Arg)SNV Uncertain significance 166574 rs727503747 4:6296771-6296771 4:6295044-6295044
41 WFS1 NM_006005.3(WFS1):c.1957C>T (p.Arg653Cys)SNV Uncertain significance 178597 rs201064551 4:6303479-6303479 4:6301752-6301752
42 WFS1 NM_006005.3(WFS1):c.1396G>A (p.Gly466Ser)SNV Uncertain significance 166589 rs727503750 4:6302918-6302918 4:6301191-6301191
43 WFS1 NM_006005.3(WFS1):c.2029G>A (p.Ala677Thr)SNV Uncertain significance 198834 rs757027394 4:6303551-6303551 4:6301824-6301824
44 WFS1 NM_006005.3(WFS1):c.1724C>G (p.Ala575Gly)SNV Uncertain significance 440419 rs71524360 4:6303246-6303246 4:6301519-6301519
45 WFS1 NM_006005.3(WFS1):c.1124G>A (p.Arg375His)SNV Uncertain significance 504709 rs142671083 4:6302646-6302646 4:6300919-6300919
46 WFS1 NM_006005.3(WFS1):c.2171C>T (p.Pro724Leu)SNV Uncertain significance 4509 rs28937890 4:6303693-6303693 4:6301966-6301966
47 WFS1 NM_006005.3(WFS1):c.1633G>A (p.Val545Met)SNV Uncertain significance 215391 rs201993978 4:6303155-6303155 4:6301428-6301428
48 WFS1 NM_006005.3(WFS1):c.535G>A (p.Ala179Thr)SNV Uncertain significance 229647 rs776685250 4:6292998-6292998 4:6291271-6291271
49 WFS1 NM_006005.3(WFS1):c.1079G>A (p.Cys360Tyr)SNV Uncertain significance 374398 rs147157374 4:6302601-6302601 4:6300874-6300874
50 WFS1 NM_006005.3(WFS1):c.2191A>G (p.Met731Val)SNV Uncertain significance 374399 rs144010362 4:6303713-6303713 4:6301986-6301986

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 endoplasmic reticulum membrane GO:0005789 9.73 WFS1 SYVN1 HSPA5 CISD2 CDKAL1 ATF6
2 intracellular membrane-bounded organelle GO:0043231 9.43 PCSK2 NCS1 HSPA5 CISD3 CISD2 CISD1
3 secretory granule GO:0030141 9.33 SCG5 PCSK2 AVP
4 integral component of endoplasmic reticulum membrane GO:0030176 8.92 WFS1 SYVN1 HSPA5 ATF6

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 visual perception GO:0007601 9.62 WFS1 EFEMP1 CRYAA ATF6
2 ubiquitin-dependent ERAD pathway GO:0030433 9.54 WFS1 SYVN1 HSPA5
3 peptide hormone processing GO:0016486 9.51 SCG5 PCSK2
4 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 9.49 WFS1 SYVN1
5 synaptic transmission, dopaminergic GO:0001963 9.48 DRD5 CRH
6 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress GO:1990440 9.46 HSPA5 ATF6
7 ER overload response GO:0006983 9.43 WFS1 HSPA5
8 IRE1-mediated unfolded protein response GO:0036498 9.43 WFS1 SYVN1 HSPA5
9 ATF6-mediated unfolded protein response GO:0036500 9.4 HSPA5 ATF6
10 response to cocaine GO:0042220 9.33 HSPA5 DRD5 CRH
11 negative regulation of NAD(P)H oxidase activity GO:0033861 8.96 INS DRD5
12 endoplasmic reticulum unfolded protein response GO:0030968 8.92 WFS1 SYVN1 HSPA5 ATF6

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

# Name GO ID Score Top Affiliating Genes
1 unfolded protein binding GO:0051082 9.46 SYVN1 SCG5 HSPA5 CRYAA
2 hormone activity GO:0005179 9.43 INS CRH AVP
3 2 iron, 2 sulfur cluster binding GO:0051537 9.13 CISD3 CISD2 CISD1
4 iron-sulfur cluster binding GO:0051536 8.92 CISD3 CISD2 CISD1 CDKAL1

Sources for Wolfram Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
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72 UMLS via Orphanet
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