WFS2
MCID: WLF009
MIFTS: 35

Wolfram Syndrome 2 (WFS2)

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

Aliases & Classifications for Wolfram Syndrome 2

MalaCards integrated aliases for Wolfram Syndrome 2:

Name: Wolfram Syndrome 2 58 12 76 30 13 6 15 74
Wfs2 58 12 76
Wolfram Syndrome, Type 2 41

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in the first or second decade of life


HPO:

33
wolfram syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Wolfram Syndrome 2

Disease Ontology : 12 An autosomal recessive neurodegenerative disorder characterized by diabetes mellitus, high frequency sensorineural hearing loss, optic atrophy or neuropathy, and defective platelet aggregation resulting in peptic ulcer bleeding. It has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the CISD2 gene on chromosome 4q24.

MalaCards based summary : Wolfram Syndrome 2, also known as wfs2, is related to wolfram syndrome and optic nerve disease. An important gene associated with Wolfram Syndrome 2 is CISD2 (CDGSH Iron Sulfur Domain 2). The drugs Acetylcysteine and Deferiprone have been mentioned in the context of this disorder. Affiliated tissues include eye, and related phenotypes are gastric ulcer and depressivity

OMIM : 58 Wolfram syndrome-2 is an autosomal recessive neurodegenerative disorder characterized by diabetes mellitus, high frequency sensorineural hearing loss, optic atrophy or neuropathy, and defective platelet aggregation resulting in peptic ulcer bleeding (summary by Mozzillo et al., 2014). For a discussion of genetic heterogeneity of Wolfram syndrome, see WFS1 (222300). (604928)

UniProtKB/Swiss-Prot : 76 Wolfram syndrome 2: A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent.

Related Diseases for Wolfram Syndrome 2

Diseases in the Wolfram Syndrome family:

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

Diseases related to Wolfram Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 wolfram syndrome 30.0 CISD2 TOMM40 WFS1
2 optic nerve disease 29.8 CISD2 WFS1
3 waardenburg syndrome, type 1 10.0 CISD2 WFS1
4 deafness, autosomal dominant 6 10.0 CISD2 WFS1
5 neuropathy 10.0
6 diabetes insipidus 10.0 CISD2 WFS1
7 wolfram syndrome 1 9.9
8 3-methylglutaconic aciduria, type iii 9.8 CISD2 WFS1

Graphical network of the top 20 diseases related to Wolfram Syndrome 2:



Diseases related to Wolfram Syndrome 2

Symptoms & Phenotypes for Wolfram Syndrome 2

Human phenotypes related to Wolfram Syndrome 2:

33 (show all 8)
# Description HPO Frequency HPO Source Accession
1 gastric ulcer 33 occasional (7.5%) HP:0002592
2 depressivity 33 HP:0000716
3 diabetes mellitus 33 HP:0000819
4 sensorineural hearing impairment 33 HP:0000407
5 optic atrophy 33 HP:0000648
6 abnormal bleeding 33 HP:0001892
7 optic neuropathy 33 HP:0001138
8 impaired collagen-induced platelet aggregation 33 HP:0008320

Symptoms via clinical synopsis from OMIM:

58
Endocrine Features:
diabetes mellitus

Neurologic Behavioral Psychiatric Manifestations:
depression (in some patients)

Abdomen Gastrointestinal:
peptic ulcer disease (in some patients)

Hematology:
bleeding associated with peptic ulcer disease
defective platelet aggregation in response to adp

Head And Neck Eyes:
optic neuropathy
optic atrophy (may be asymptomatic in some patients)

Head And Neck Ears:
sensorineural hearing loss, high frequency

Genitourinary Kidneys:
urinary tract dilatation (in some patients)
impaired renal function (in some patients)

Clinical features from OMIM:

604928

Drugs & Therapeutics for Wolfram Syndrome 2

Drugs for Wolfram Syndrome 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 26)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcysteine Approved, Investigational Phase 2, Phase 3 616-91-1 12035
2
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
3
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
4
Iron Approved, Experimental Phase 2, Phase 3 7439-89-6, 15438-31-0 27284 23925
5 Protective Agents Phase 2, Phase 3
6 Free Radical Scavengers Phase 2, Phase 3
7 Incretins Phase 2, Phase 3
8 Iron Chelating Agents Phase 2, Phase 3
9 Sitagliptin Phosphate Phase 2, Phase 3
10 Anti-Infective Agents Phase 2, Phase 3
11 HIV Protease Inhibitors Phase 2, Phase 3
12 Antidotes Phase 2, Phase 3
13 Hormone Antagonists Phase 2, Phase 3
14
protease inhibitors Phase 2, Phase 3
15 Hypoglycemic Agents Phase 2, Phase 3
16 Chelating Agents Phase 2, Phase 3
17 Respiratory System Agents Phase 2, Phase 3
18 Hormones Phase 2, Phase 3
19 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
20 Antioxidants Phase 2, Phase 3
21 N-monoacetylcystine Phase 2, Phase 3
22 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3
23 Expectorants Phase 2, Phase 3
24 Antiviral Agents Phase 2, Phase 3
25 Insulin, Globin Zinc
26 insulin

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 Wolfram Syndrome International Registry and Clinical Study Recruiting NCT02841553
3 Tracking Neurodegeneration in Early Wolfram Syndrome Completed NCT02455414

Search NIH Clinical Center for Wolfram Syndrome 2

Genetic Tests for Wolfram Syndrome 2

Genetic tests related to Wolfram Syndrome 2:

# Genetic test Affiliating Genes
1 Wolfram Syndrome 2 30 CISD2

Anatomical Context for Wolfram Syndrome 2

MalaCards organs/tissues related to Wolfram Syndrome 2:

42
Eye

Publications for Wolfram Syndrome 2

Articles related to Wolfram Syndrome 2:

# Title Authors Year
1
Wolfram syndrome 2: a novel CISD2 mutation identified in Italian siblings. ( 25371195 )
2015
2
A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2. ( 25056293 )
2014
3
Wolfram syndrome 1 and Wolfram syndrome 2. ( 22790102 )
2012
4
Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2. ( 19580816 )
2009
5
Mitochondrial abnormalities drive cell death in Wolfram syndrome 2. ( 19648948 )
2009
6
A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. ( 17846994 )
2007
7
Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q. ( 10739754 )
2000

Variations for Wolfram Syndrome 2

ClinVar genetic disease variations for Wolfram Syndrome 2:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CISD2 NM_001008388.4(CISD2): c.109G> C (p.Glu37Gln) single nucleotide variant Pathogenic rs63749888 GRCh37 Chromosome 4, 103806378: 103806378
2 CISD2 NM_001008388.4(CISD2): c.109G> C (p.Glu37Gln) single nucleotide variant Pathogenic rs63749888 GRCh38 Chromosome 4, 102885221: 102885221
3 CISD2 NM_001008388.4(CISD2): c.(104_304)-84_318+724del deletion Pathogenic GRCh38 Chromosome 4, 102885132: 102887186

Expression for Wolfram Syndrome 2

Search GEO for disease gene expression data for Wolfram Syndrome 2.

Pathways for Wolfram Syndrome 2

GO Terms for Wolfram Syndrome 2

Cellular components related to Wolfram Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial outer membrane GO:0005741 8.96 CISD2 TOMM40
2 mitochondrion GO:0005739 8.8 ATP2A1 CISD2 TOMM40

Biological processes related to Wolfram Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of neuron apoptotic process GO:0043524 8.96 PPT1 WFS1
2 response to endoplasmic reticulum stress GO:0034976 8.62 ATP2A1 WFS1

Sources for Wolfram Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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