WFS2
MCID: WLF009
MIFTS: 42

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 56 12 73 29 13 6 15 71
Wfs2 56 12 73
Wolfram Syndrome, Type 2 39

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in the first or second decade of life
rheumatologic manifestations, including lofgren syndrome, have been reported in some patients


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 1 and wolfram syndrome. An important gene associated with Wolfram Syndrome 2 is CISD2 (CDGSH Iron Sulfur Domain 2), and among its related pathways/superpathways are Apelin signaling pathway and Spinocerebellar ataxia. The drugs Acetylcysteine and Iron have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, and related phenotypes are gastric ulcer and sensorineural hearing impairment

OMIM : 56 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 : 73 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

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:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 gastric ulcer 31 occasional (7.5%) HP:0002592
2 sensorineural hearing impairment 31 HP:0000407
3 optic atrophy 31 HP:0000648
4 primary amenorrhea 31 HP:0000786
5 depressivity 31 HP:0000716
6 diabetes mellitus 31 HP:0000819
7 abnormal bleeding 31 HP:0001892
8 optic neuropathy 31 HP:0001138
9 neurogenic bladder 31 HP:0000011
10 oligomenorrhea 31 HP:0000876
11 impaired collagen-induced platelet aggregation 31 HP:0008320
12 decreased circulating antibody level 31 HP:0004313

Symptoms via clinical synopsis from OMIM:

56
Genitourinary Internal Genitalia Female:
primary amenorrhea
oligomenorrhea
delayed menarch

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

Immunology:
hypogammaglobulinemia

Head And Neck Ears:
sensorineural hearing loss, high frequency

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

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

Endocrine Features:
diabetes mellitus

Genitourinary Bladder:
neurogenic bladder

Neurologic Behavioral Psychiatric Manifestations:
depression (in some patients)

Abdomen Gastrointestinal:
peptic ulcer disease (in some patients)

Skeletal Spine:
spondyloarthritis, hla-b27+

Clinical features from OMIM:

604928

MGI Mouse Phenotypes related to Wolfram Syndrome 2:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.23 BECN1 CISD2 ITPR1 ITPR3 MNT PPIA

Drugs & Therapeutics for Wolfram Syndrome 2

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

(show all 22)
# 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 Respiratory System Agents Phase 2, Phase 3
6 Hormones Phase 2, Phase 3
7 Hormone Antagonists Phase 2, Phase 3
8 Antidotes Phase 2, Phase 3
9 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
10 Hypoglycemic Agents Phase 2, Phase 3
11 Antioxidants Phase 2, Phase 3
12 Chelating Agents Phase 2, Phase 3
13 Anti-Infective Agents Phase 2, Phase 3
14
protease inhibitors Phase 2, Phase 3
15 Antiviral Agents Phase 2, Phase 3
16 Iron Chelating Agents Phase 2, Phase 3
17 HIV Protease Inhibitors Phase 2, Phase 3
18 Sitagliptin Phosphate Phase 2, Phase 3
19 Incretins Phase 2, Phase 3
20 Protective Agents Phase 2, Phase 3
21 Expectorants Phase 2, Phase 3
22 N-monoacetylcystine Phase 2, Phase 3

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

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:

40
Skeletal Muscle

Publications for Wolfram Syndrome 2

Articles related to Wolfram Syndrome 2:

(show all 33)
# Title Authors PMID Year
1
Wolfram syndrome 2: a novel CISD2 mutation identified in Italian siblings. 6 56 61
25371195 2015
2
A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2. 6 56 61
25056293 2014
3
A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. 6 61 56
17846994 2007
4
Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q. 6 56
10739754 2000
5
A donor splice site mutation in CISD2 generates multiple truncated, non-functional isoforms in Wolfram syndrome type 2 patients. 6 61
29237418 2017
6
Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. 56 61
19451219 2009
7
Homozygosity mapping and direct sequencing identify a novel pathogenic variant in the CISD2 gene in an Iranian Wolfram syndrome family. 61
31309279 2020
8
Clinical and molecular assessment of 13 Iranian families with Wolfram syndrome. 61
31313226 2019
9
Wolfram syndrome, a rare neurodegenerative disease: from pathogenesis to future treatment perspectives. 61
31337416 2019
10
The cisd gene family regulates physiological germline apoptosis through ced-13 and the canonical cell death pathway in Caenorhabditis elegans. 61
29666474 2019
11
[Screening for ocular involvement in deaf children]. 61
31565135 2019
12
Correction: Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease. 61
30171196 2018
13
Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease. 61
29774890 2018
14
Comparative proteomic profiling reveals a role for Cisd2 in skeletal muscle aging. 61
29168286 2018
15
Generation of Human-Induced Pluripotent Stem Cells from Wolfram Syndrome Type 2 Patients Bearing the c.103 + 1G>A CISD2 Mutation for Disease Modeling. 61
29239282 2018
16
A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca2+ homeostasis and ER-mitochondria interactions. 61
28335035 2017
17
Binding of Nitric Oxide in CDGSH-type [2Fe-2S] Clusters of the Human Mitochondrial Protein Miner2. 61
28082676 2017
18
Previously unreported abnormalities in Wolfram Syndrome Type 2. 61
29073294 2017
19
Dysregulation of Mitochondrial Functions and Osteogenic Differentiation in Cisd2-Deficient Murine Induced Pluripotent Stem Cells. 61
26230298 2015
20
Structure-function analysis of NEET proteins uncovers their role as key regulators of iron and ROS homeostasis in health and disease. 61
25448035 2015
21
A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome. 61
25422446 2014
22
Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease. 61
24705017 2014
23
Nutrient-deprivation autophagy factor-1 (NAF-1): biochemical properties of a novel cellular target for anti-diabetic drugs. 61
23717386 2013
24
Wolfram syndrome 1 and Wolfram syndrome 2. 61
22790102 2012
25
Bcl-2-associated autophagy regulator Naf-1 required for maintenance of skeletal muscle. 61
22343142 2012
26
BCL2-CISD2: An ER complex at the nexus of autophagy and calcium homeostasis? 61
22617439 2012
27
A role for the CISD2 gene in lifespan control and human disease. 61
20649540 2010
28
Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. 61
20010695 2010
29
Cisd2 mediates mitochondrial integrity and life span in mammals. 61
19717971 2009
30
Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2. 61
19580816 2009
31
Mitochondrial abnormalities drive cell death in Wolfram syndrome 2. 61
19648948 2009
32
Wolfram syndrome: identification of a phenotypic and genotypic variant from Jordan. 61
12116178 2002
33
Bleeding tendency in Wolfram syndrome: a newly identified feature with phenotype genotype correlation. 61
11317648 2001

Variations for Wolfram Syndrome 2

ClinVar genetic disease variations for Wolfram Syndrome 2:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CISD2 NM_001008388.5(CISD2):c.103+1G>ASNV Pathogenic 638297 4:103790345-103790345 4:102869188-102869188
2 CISD2 NM_001008388.5(CISD2):c.109G>C (p.Glu37Gln)SNV Pathogenic 892 rs63749888 4:103806378-103806378 4:102885221-102885221
3 CISD2 NM_001008388.4(CISD2):c.(104_304)-84_318+724deldeletion Pathogenic 156218 4:102885132-102887186

Expression for Wolfram Syndrome 2

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

Pathways for Wolfram Syndrome 2

Pathways related to Wolfram Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.27 ITPR3 ITPR1 BECN1
2 10.92 ITPR3 ITPR1 BECN1
3 10.8 ITPR3 ITPR1
4
Show member pathways
10.66 ITPR3 ITPR1

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 9.55 WFS1 ITPR3 ITPR1 CISD2 BECN1
2 mitochondrial outer membrane GO:0005741 9.13 TOMM40 CISD2 CISD1
3 platelet dense tubular network membrane GO:0031095 8.62 ITPR3 ITPR1

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

# Name GO ID Score Top Affiliating Genes
1 autophagy of mitochondrion GO:0000422 9.16 CISD2 BECN1
2 endoplasmic reticulum calcium ion homeostasis GO:0032469 8.96 WFS1 ITPR1
3 inositol phosphate-mediated signaling GO:0048016 8.62 ITPR3 ITPR1

Molecular functions related to Wolfram Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 iron-sulfur cluster binding GO:0051536 9.33 CISD3 CISD2 CISD1
2 inositol 1,4,5 trisphosphate binding GO:0070679 9.32 ITPR3 ITPR1
3 calcium-release channel activity GO:0015278 9.26 ITPR3 ITPR1
4 inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity GO:0005220 8.96 ITPR3 ITPR1
5 2 iron, 2 sulfur cluster binding GO:0051537 8.8 CISD3 CISD2 CISD1

Sources for Wolfram Syndrome 2

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
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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