MCID: WLF009
MIFTS: 34

Wolfram Syndrome 2

Categories: Genetic diseases, Eye diseases, Ear diseases, Endocrine diseases, Fetal 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 wolfram syndrome 1. An important gene associated with Wolfram Syndrome 2 is CISD2 (CDGSH Iron Sulfur Domain 2). The drugs Metformin and Deferiprone have been mentioned in the context of this disorder. Related phenotypes are sensorineural hearing impairment and optic atrophy

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 28.8 CISD2 TOMM40 WFS1
2 wolfram syndrome 1 9.8
3 diabetes insipidus 9.7 CISD2 WFS1
4 3-methylglutaconic aciduria, type iii 9.4 CISD2 WFS1

Symptoms & Phenotypes for Wolfram Syndrome 2

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
sensorineural hearing loss, high frequency

Abdomen Gastrointestinal:
peptic ulcer disease (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
depression (in some patients)

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

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

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

Endocrine Features:
diabetes mellitus


Clinical features from OMIM:

604928

Human phenotypes related to Wolfram Syndrome 2:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 32 HP:0000407
2 optic atrophy 32 HP:0000648
3 depressivity 32 HP:0000716
4 diabetes mellitus 32 HP:0000819
5 optic neuropathy 32 HP:0001138
6 abnormal bleeding 32 HP:0001892
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 25)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
2
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
3
Iron Approved Phase 2, Phase 3 7439-89-6 23925
4
Acetylcysteine Approved, Investigational Phase 2, Phase 3 616-91-1 12035
5
protease inhibitors Phase 2, Phase 3
6 Respiratory System Agents Phase 2, Phase 3
7 Chelating Agents Phase 2, Phase 3
8 Sitagliptin Phosphate Phase 2, Phase 3
9 HIV Protease Inhibitors Phase 2, Phase 3
10 N-monoacetylcystine Phase 2, Phase 3
11 Hormone Antagonists Phase 2, Phase 3
12 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
13 Hormones Phase 2, Phase 3
14 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3
15 Hypoglycemic Agents Phase 2, Phase 3
16 Expectorants Phase 2, Phase 3
17 Antidotes Phase 2, Phase 3
18 Incretins Phase 2, Phase 3
19 Anti-Infective Agents Phase 2, Phase 3
20 Iron Chelating Agents Phase 2, Phase 3
21 Antioxidants Phase 2, Phase 3
22 Protective Agents Phase 2, Phase 3
23 Antiviral Agents 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 Active, not 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 29 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.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 9.13 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
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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