WFS2
MCID: WLF009
MIFTS: 36

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 57 12 75 29 13 6 15 73
Wfs2 57 12 75
Wolfram Syndrome, Type 2 40

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in the first or second decade of life


HPO:

32
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 Iron and Metformin have been mentioned in the context of this disorder. Affiliated tissues include eye, and related phenotypes are depressivity and diabetes mellitus

OMIM : 57 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 : 75 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 30.2 CISD2 TOMM40 WFS1
2 optic nerve disease 29.9 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 9.9 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Wolfram Syndrome 2:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 depressivity 32 HP:0000716
2 diabetes mellitus 32 HP:0000819
3 sensorineural hearing impairment 32 HP:0000407
4 optic atrophy 32 HP:0000648
5 abnormal bleeding 32 HP:0001892
6 optic neuropathy 32 HP:0001138
7 gastric ulcer 32 occasional (7.5%) HP:0002592
8 impaired collagen-induced platelet aggregation 32 HP:0008320

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
Iron Approved Phase 2, Phase 3 7439-89-6 23925
2
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
3
Acetylcysteine Approved, Investigational Phase 2, Phase 3 616-91-1 12035
4
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
5 Hormone Antagonists Phase 2, Phase 3
6
protease inhibitors Phase 2, Phase 3
7 Hormones Phase 2, Phase 3
8 HIV Protease Inhibitors Phase 2, Phase 3
9 Incretins Phase 2, Phase 3
10 Protective Agents Phase 2, Phase 3
11 Antioxidants Phase 2, Phase 3
12 Anti-Infective Agents Phase 2, Phase 3
13 Expectorants Phase 2, Phase 3
14 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3
15 N-monoacetylcystine Phase 2, Phase 3
16 Sitagliptin Phosphate Phase 2, Phase 3
17 Respiratory System Agents Phase 2, Phase 3
18 Free Radical Scavengers Phase 2, Phase 3
19 Hypoglycemic Agents Phase 2, Phase 3
20 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
21 Iron Chelating Agents Phase 2, Phase 3
22 Antiviral Agents Phase 2, Phase 3
23 Antidotes Phase 2, Phase 3
24 Chelating 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 29 CISD2

Anatomical Context for Wolfram Syndrome 2

MalaCards organs/tissues related to Wolfram Syndrome 2:

41
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 )
2014
2
Wolfram syndrome 1 and Wolfram syndrome 2. ( 22790102 )
2012
3
Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2. ( 19580816 )
2009
4
Mitochondrial abnormalities drive cell death in Wolfram syndrome 2. ( 19648948 )
2009
5
A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. ( 17846994 )
2007

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 endoplasmic reticulum membrane GO:0005789 9.33 ATP2A1 CISD2 WFS1
2 mitochondrial outer membrane GO:0005741 8.96 CISD2 TOMM40
3 mitochondrion GO:0005739 8.92 ATP2A1 CISD2 PPIA TOMM40

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

# Name GO ID Score Top Affiliating Genes
1 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 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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