MCID: WLF009
MIFTS: 33

Wolfram Syndrome 2

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

Aliases & Classifications for Wolfram Syndrome 2

MalaCards integrated aliases for Wolfram Syndrome 2:

Name: Wolfram Syndrome 2 53 12 71 28 13 14 69
Wfs2 53 12 71

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in the first or second decade of life


HPO:

31
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 diabetes insipidus, and has symptoms including diabetes mellitus, sensorineural hearing impairment and optic atrophy. 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.

OMIM : 53 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 : 71 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 29.3 CISD2 TOMM40 WFS1
2 diabetes insipidus 9.8 CISD2 WFS1
3 wolfram syndrome 1 9.8
4 3-methylglutaconic aciduria, type iii 9.6 CISD2 WFS1

Symptoms & Phenotypes for Wolfram Syndrome 2

Symptoms via clinical synopsis from OMIM:

53
HeadAndNeckEars:
sensorineural hearing loss, high frequency

AbdomenGastrointestinal:
peptic ulcer disease (in some patients)

NeurologicBehavioralPsychiatricManifestations:
depression (in some patients)

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

HeadAndNeckEyes:
optic atrophy (may be asymptomatic in some patients)
optic neuropathy

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

EndocrineFeatures:
diabetes mellitus


Clinical features from OMIM:

604928

Human phenotypes related to Wolfram Syndrome 2:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 diabetes mellitus 31 HP:0000819
2 sensorineural hearing impairment 31 HP:0000407
3 optic atrophy 31 HP:0000648
4 abnormal bleeding 31 HP:0001892
5 gastric ulcer 31 occasional (7.5%) HP:0002592
6 optic neuropathy 31 HP:0001138
7 depressivity 31 HP:0000716
8 impaired collagen-induced platelet aggregation 31 HP:0008320

Drugs & Therapeutics for Wolfram Syndrome 2

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

(show all 25)
# 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
Iron Approved Phase 2, Phase 3 7439-89-6 23925
4
Metformin Approved Phase 2, Phase 3 657-24-9 4091 14219
5 Antidotes Phase 2, Phase 3
6 Anti-Infective Agents Phase 2, Phase 3
7 Antioxidants Phase 2, Phase 3
8 Antiviral Agents Phase 2, Phase 3
9 Chelating Agents Phase 2, Phase 3
10 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
11 Expectorants Phase 2, Phase 3
12 HIV Protease Inhibitors Phase 2, Phase 3
13 Hormone Antagonists Phase 2, Phase 3
14 Hormones Phase 2, Phase 3
15 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3
16 Hypoglycemic Agents Phase 2, Phase 3
17 Incretins Phase 2, Phase 3
18 Iron Chelating Agents Phase 2, Phase 3
19 N-monoacetylcystine Phase 2, Phase 3
20
protease inhibitors Phase 2, Phase 3
21 Protective Agents Phase 2, Phase 3
22 Respiratory System Agents Phase 2, Phase 3
23 Sitagliptin Phosphate Phase 2, Phase 3
24 insulin
25 Insulin, Globin Zinc

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy Not yet recruiting 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 Recruiting 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 28 CISD2

Anatomical Context for Wolfram Syndrome 2

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.(104_304)-84_318+724del deletion Pathogenic GRCh38 Chromosome 4, 102885132: 102887186
2 CISD2 NM_001008388.4(CISD2): c.109G> C (p.Glu37Gln) single nucleotide variant Pathogenic rs63749888 GRCh37 Chromosome 4, 103806378: 103806378

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 9.13 ATP2A1 CISD2 WFS1
2 mitochondrial outer membrane GO:0005741 8.62 CISD2 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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