WS
MCID: WRN001
MIFTS: 75

Werner Syndrome (WS) malady

Eye diseases, Skin diseases, Fetal diseases, Cancer diseases categories

Summaries for Werner Syndrome

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21Genetics Home Reference, 42NIH Rare Diseases, 63Wikipedia, 46OMIM, 19GeneReviews, 32MalaCards
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NIH Rare Diseases:42 Werner's syndrome is a disease chiefly characterized by premature aging and cancer predisposition. development is typically normal until the end of the first decade; the first sign is the lack of a growth spurt during puberty. early signs (usually in the 20s) include loss and graying of hair, hoarseness, and scleroderma-like skin changes, followed by cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers, and osteoporosis in the 30s. myocardial infarction (heart attack) and cancer are the most common causes of death, which typically occurs in the late 40s. it is caused by mutations in the wrn gene and is inherited in an autosomal recessive manner. management focuses on treatment of signs and symptoms and prevention of secondary complications. last updated: 4/29/2011

MalaCards: Werner Syndrome, also known as werner's syndrome, is related to progeria and rapadilino syndrome, and has symptoms including thyroid neoplasm/tumor/carcinoma/cancer, white forelock/piebaldism and oropharyngeal neoplasm/tumor/carcinoma/cancer. An important gene associated with Werner Syndrome is WRN (Werner syndrome, RecQ helicase-like), and among its related pathways are Nucleotide Excision Repair and Homologous recombination. The compounds methylmethanesulfonate and hydroxyurea have been mentioned in the context of this disorder. Affiliated tissues include skin, heart and breast, and related mouse phenotypes are cellular and mortality/aging.

Genetics Home Reference:21 Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature. The characteristic aged appearance of individuals with Werner syndrome typically begins to develop when they are in their twenties and includes graying and loss of hair; a hoarse voice; and thin, hardened skin. They may also have a facial appearance described as "bird-like." Many people with Werner syndrome have thin arms and legs and a thick trunk due to abnormal fat deposition.

Wikipedia:63 Werner syndrome (WS), also known as \"adult progeria\", is a rare, autosomal recessiveprogeroid syndrome... more...

Description from OMIM:46 277700

GeneReviews summary for werner

Aliases & Classifications for Werner Syndrome

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8Disease Ontology, 9diseasecard, 19GeneReviews, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 60UMLS, 20GeneTests, 22GTR, 56SNOMED-CT, 34MeSH, 39NCIt, 35MESH via Orphanet, 26ICD10 via Orphanet, 57SNOMED-CT via Orphanet, 61UMLS via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Fetal diseases, Cancer diseases
Anatomical: Eye diseases, Skin diseases


Characteristics (Orphanet epidemiological data):

48
werner syndrome:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000; Age of onset: Adolescence / Young adulthood


Aliases & Descriptions:

werner syndrome 8 9 19 42 21 46 10 44 48 60
werner's syndrome 8 42 20 22 21
adult progeria 8 21 48
ws 8 21 48
adult premature ageing syndrome 8
adult premature aging syndrome 21
werners syndrome 21
wrn 42


External Ids:

Disease Ontology8 DOID:5688
OMIM46 277700
MeSH34 D014898
NCIt39 C3447
MESH via Orphanet35 D014898
ICD10 via Orphanet26 E34.8
SNOMED-CT via Orphanet57 51626007
UMLS via Orphanet61 C0043119

Related Diseases for Werner Syndrome

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17GeneCards, 18GeneDecks
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Diseases related to Werner Syndrome via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 110)
idRelated DiseaseScoreTop Affiliating Genes
1progeria30.8LMNA, WRN, HELLS
2rapadilino syndrome30.4WRN, RECQL, RECQL4, RECQL5
3bloom syndrome30.3TERF2, RAD54L, RECQL5, RECQL4, RECQL, BLM
4ataxia telangiectasia30.3RPA1, HELLS, WRN, BLM, TERF2
5nijmegen breakage syndrome30.2TERF2, BLM, WRN, RPA1
6rothmund-thomson syndrome30.2HELLS, WRN, BLM, RECQL, RECQL4, RECQL5
7multiple sclerosis30.0RPA1
8xeroderma pigmentosum29.9RPA1, HELLS, FEN1, RECQL, RAD54L
9leukemia29.9RPA1, HELLS, GYPA, POLB, DNASE1, RECQL4
10breast cancer29.9RPA1, HELLS, FEN1, WRN, POLB, DNASE1
11pancreatic cancer29.9DNASE1
12cataract29.9WRN, RECQL4
13williams syndrome10.5
14adult syndrome10.4
15n syndrome10.4
16atypical werner syndrome10.4
17waardenburg syndrome type i10.3
18meningioma10.3
19waardenburg syndrome type 310.2
20waardenburg syndrome type 2a10.2
21waardenburg syndrome type iva10.2
22spondylosis10.2
23senile cataract10.2
24colorectal cancer10.2
25down syndrome10.2
26osteosarcoma10.2
27coronary artery disease10.1
28fanconi syndrome10.1
29hyperglycemia10.1
30sarcoma10.1
31thyroiditis10.1
32chronic myeloid leukemia10.1
33adenocarcinoma10.1
34esophageal cancer10.1
35esophagitis10.1
36gastric adenocarcinoma10.1
37myeloid leukemia10.1
38prostate cancer10.1
39prostatitis10.1
40bile reflux10.1
41waardenburg syndrome type 210.1
42waardenburg syndrome type ivb10.1
43waardenburg syndrome type ivc10.1
44waardenburg syndrome type iid10.1
45waardenburg syndrome, type 2e, with or without neurologic involvement10.1
46non-hodgkin lymphoma10.0
47protein s deficiency10.0
48diffuse large b-cell lymphoma10.0
49cervical cancer10.0
50cervicitis10.0

Graphical network of the top 20 diseases related to Werner Syndrome:



Diseases related to werner syndrome

Clinical Features for Werner Syndrome

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46OMIM, 48Orphanet
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Clinical features from OMIM:

277700

Clinical synopsis from OMIM:

277700

Symptoms:

48 (show all 56)
  • thyroid neoplasm/tumor/carcinoma/cancer
  • white forelock/piebaldism
  • oropharyngeal neoplasm/tumor/carcinoma/cancer
  • skin/cutaneous neoplasm/tumor/carcinoma/cancer (excluding melanoma)
  • small hand/acromicria
  • meningioma
  • digestive neoplasm/tumor/carcinoma/cancer
  • ovary/fallopian tube neoplasm/tumor/carcinoma/cancer (excl. teratoma/germinoma)
  • breast neoplasm/tumor/carcinoma/cancer
  • global upper and lower limbs anomalies
  • arterial atheroma/precocious atherosclerosis/arteriosclerosis
  • short stature/dwarfism/nanism
  • small bowel neoplasm/tumor/carcinoma/cancer
  • oral cavity/tongue neoplasm/tumor/carcinoma/cancer
  • abnormal fall of hair
  • pili torti
  • abnormal fat distribution/lipodystrophy
  • arterial pulse abolition
  • testis anomalies
  • pes talus
  • beaked nose
  • pulmonary artery stenosis/absence/hypoplasia of the pulmonary branches
  • sterility/hypofertility
  • chronic skin infection/ulcerations/ulcers/cancrum
  • osteosclerosis/osteopetrosis/bone condensation
  • lipoatrophy
  • hyperkeratosis/ainhum/hyperkeratotic skin fissures
  • muscle hypotrophy/atrophy/dystrophy/agenesis/amyotrophy
  • abnormal cry/voice/phonation disorder/nasal speech
  • laryngomalacia
  • late puberty/hypogonadism/hypogenitalism
  • retinitis pigmentosa/retinal pigmentary changes
  • restricted joint mobility/joint stiffness/ankylosis
  • cataract/lens opacification
  • osteoporosis/osteopenia/demineralisation/osteomalacia/rickets
  • diabetes mellitus
  • chronic arterial hypertension
  • autosomal dominant inheritance
  • telangiectasiae of the skin
  • anomalies of chest/thorax/trunk
  • sarcoma
  • skin hypoplasia/aplasia/atrophy
  • premature ageing
  • narrow face
  • neoplasms/tumors
  • kidney/renal neoplasm/tumor/carcinoma/cancer
  • cerebral vascular anomalies
  • hypotrichosis/atrichia/atrichiasis/scalp hairlessness
  • small/atrophic/hypoplastic testes/monorchism/microorchidism/anorchia
  • precocious menopause/secondary amenorrhea
  • lung/bronchopulmonary neoplasm/tumor/carcinoma/cancer
  • periarticular tissue anomaly/extraarticular calcifications
  • angor pectoris/myocardial infarction
  • heart/cardiac failure
  • tight skin/lack of elasticity
  • autosomal recessive inheritance

Drugs & Therapeutics for Werner Syndrome

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Sources:
5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-RT
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Approved drugs:

Search CenterWatch for Werner Syndrome

Drug clinical trials:

Search ClinicalTrials for Werner Syndrome

Search NIH Clinical Center for Werner Syndrome

Search CenterWatch for Werner Syndrome

Genetic Tests for Werner Syndrome

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20GeneTests, 22GTR
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Genetic tests related to Werner Syndrome:

id Genetic test Affiliating Genes
1 Werner Syndrome20 22 WRN

Anatomical Context for Werner Syndrome

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32MalaCards
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MalaCards organs/tissues related to Werner Syndrome:

32
Skin, Heart, Breast, Thyroid, Lung, Kidney, Ovary, Testis, Testes, Bone, Tongue, Eye, Uterus, Liver

Animal Models for Werner Syndrome or affiliated genes

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36MGI
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MGI Mouse Phenotypes related to Werner Syndrome:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:000538410.5TERF2, RPA1, EXO1, HELLS, FEN1, WRN
2MP:001076810.5TREX1, WRN, FEN1, HELLS, EXO1, RPA1
3MP:001077110.5RECQL4, BLM, POLB, TREX1, WRN
4MP:000538710.5RPA1, EXO1, HELLS, FEN1, WRN, TREX1
5MP:000539710.4RPA1, EXO1, HELLS, FEN1, TREX1, POLB
6MP:000200610.2RPA1, BLM, RECQL4

Publications for Werner Syndrome

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50PubMed
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Articles related to Werner Syndrome:

(show top 50)    (show all 433)
idTitleAuthorsYear
1
Serines 440 and 467 in the Werner syndrome protein are phosphorylated by DNA-PK and affects its dynamics in response to DNA double strand breaks. (24429382)
2014
2
Sitagliptin improves postprandial hyperglycemia by inhibiting glucagon secretion in Werner syndrome with diabetes. (23881973)
2013
3
Spectrum and risk of neoplasia in Werner syndrome: a systematic review. (23573208)
2013
4
Expression of werner syndrome gene in hypothalamic neurons in physiological aging. (24385166)
2013
5
Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome. (23257959)
2013
6
Incidence and characteristics of metabolic disorders and vascular complications in individuals with Werner syndrome in Japan. (22587870)
2012
7
Herlyn-Werner-Wunderlich syndrome consisting of uterine didelphys, obstructed hemivagina and ipsilateral renal agenesis in a newborn. (22348499)
2012
8
The Werner syndrome protein: linking the replication checkpoint response to genome stability. (21389352)
2011
9
Cell cycle-regulated association between the Werner syndrome protein and its molecular partners. (21558813)
2011
10
Rapid recurrence of petroclival meningioma in Werner syndrome: case report. (21906868)
2011
11
The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) holliday junctions to functional replication forks. (21736299)
2011
12
Identification of a coiled coil in werner syndrome protein that facilitates multimerization and promotes exonuclease processivity. (20516064)
2010
13
Evaluating the role of p38 MAP kinase in growth of Werner syndrome fibroblasts. (20536832)
2010
14
A role for the Werner syndrome protein in epigenetic inactivation of the pluripotency factor Oct4. (20477760)
2010
15
Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential. (19966276)
2010
16
Telomeric protein TRF2 protects Holliday junctions with telomeric arms from displacement by the Werner syndrome helicase. (20215438)
2010
17
Secular trends towards delayed onsets of pathologies and prolonged longevities in Japanese patients with Werner syndrome. (20103906)
2008
18
Meningioma associated with Werner syndrome--case report--. (18948683)
2008
19
Elevation of soluble Fas (APO-1, CD95) ligand in natural aging and Werner syndrome. (20103915)
2008
20
Expression and localization of Werner syndrome protein is modulated by SIRT1 and PML. (17996922)
2007
21
Replication fork regression in vitro by the Werner syndrome protein (WRN): holliday junction formation, the effect of leading arm structure and a potential role for WRN exonuclease activity. (17717003)
2007
22
Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links. (16714450)
2006
23
Gene expression responses to DNA damage are altered in human aging and in Werner Syndrome. (15897889)
2005
24
Etidronate ameliorates painful soft-tissue calcification in Werner syndrome. (16274399)
2005
25
Meningioma arising in Werner syndrome confirmed by mutation analysis. (15925797)
2005
26
The Werner syndrome protein at the crossroads of DNA repair and apoptosis. (15336909)
2004
27
Dysadipocytokinemia in werner syndrome and its recovery by treatment with pioglitazone. (15451939)
2004
28
Biochemical and kinetic characterization of the DNA helicase and exonuclease activities of werner syndrome protein. (15187093)
2004
29
Central role for the Werner syndrome protein/poly(ADP-ribose) polymerase 1 complex in the poly(ADP-ribosyl)ation pathway after DNA damage. (14612404)
2003
30
Triple primary sarcoma in Werner syndrome with a novel mutation. (12771438)
2003
31
Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Werner syndrome fibroblast cells. (12899945)
2003
32
Displacement of DNA-PKcs from DNA ends by the Werner syndrome protein. (12202749)
2002
33
Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. (12181313)
2002
34
Unwinding of a DNA triple helix by the Werner and Bloom syndrome helicases. (11110789)
2001
35
Werner syndrome cells are sensitive to DNA cross-linking drugs. (11344095)
2001
36
WRN or telomerase constructs reverse 4-nitroquinoline 1-oxide sensitivity in transformed Werner syndrome fibroblasts. (10811112)
2000
37
Werner syndrome helicase contains a 5'-->3' exonuclease activity that digests DNA and RNA strands in DNA/DNA and RNA/DNA duplexes dependent on unwinding. (10325426)
1999
38
Unusual features of thyroid carcinomas in Japanese patients with Werner syndrome and possible genotype-phenotype relations to cell type and race. (10440702)
1999
39
Comparison of methods for identifying transcription units and transcription map of the Werner syndrome gene region. (9790753)
1998
40
Replication focus-forming activity 1 and the Werner syndrome gene product. (9697700)
1998
41
Unexpectedly low loss of heterozygosity in genetically unstable Werner syndrome cell lines. (9115963)
1997
42
Genetic association between chromosome 8 microsatellite (MS8-134) and Werner syndrome (WRN): chromosome microdissection and homozygosity mapping. (7490095)
1995
43
Altered regulation of fibronectin gene expression in Werner syndrome fibroblasts. (8020582)
1994
44
A genetic analysis of the Werner syndrome region on human chromosome 8p. (8325642)
1993
45
Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients. (2303247)
1990
46
Cytogenetic studies using various clastogens in two patients with Werner syndrome and control individuals. (4018799)
1985
47
Elevated spontaneous mutation rate in SV40-transformed Werner syndrome fibroblast cell lines. (2992100)
1985
48
Cell fusion studies in the Werner syndrome. (4083156)
1985
49
Abnormal fibroblast aging and DNA replication in the Werner syndrome. (4083160)
1985
50
Werner syndrome. (269694)
1977

Genetic Variations for Werner Syndrome

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62UniProtKB/Swiss-Prot
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Genetic disease variations for Werner Syndrome:

62
id Symbol AA change Variation ID SNP ID
1WRNp.Lys125AsnVAR_026588
2WRNp.Lys135GluVAR_026589

Expression for genes affiliated with Werner Syndrome

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1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Werner Syndrome

Search GEO for disease gene expression data for Werner Syndrome.

Pathways for genes affiliated with Werner Syndrome

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53Reactome, 37NCBI BioSystems Database, 29KEGG, 51QIAGEN, 4Cell Signaling Technology
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Compounds for genes affiliated with Werner Syndrome

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44Novoseek, 49PharmGKB, 11DrugBank, 28IUPHAR, 24HMDB, 59Tocris Bioscience
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Compounds related to Werner Syndrome according to GeneCards/GeneDecks:

(show all 21)
idCompoundScoreTop Affiliating Genes
1methylmethanesulfonate4410.8RPA1, HELLS, FEN1, WRN, POLB, BLM
2hydroxyurea44 49 1112.8RPA1, HELLS, WRN, BLM, DNASE1, RECQL4
3atp44 2811.8RAD54L, RPA1, EXO1, HELLS, FEN1, WRN
4magnesium44 11 2412.8HELLS, FEN1, WRN, TREX1, POLR1C, POLB
5cisplatin44 49 59 1113.8RPA1, HELLS, FEN1, WRN, POLR1C, POLB
6phosphodiester4410.8POLR1C, POLB, DNASE1
78-oxoguanine4410.8POLB, WRN, HELLS
8oligonucleotide4410.8RPA1, EXO1, HELLS, FEN1, GYPA, TREX1
9camptothecin44 59 1112.7DNASE1, BLM, WRN, RPA1
10thymine44 2411.7HELLS, POLB, DNASE1
118-hydroxyadenine4410.7WRN, HELLS
12arginine4410.7HELLS, FEN1, WRN, GYPA, POLB, LMNA
13nacl4410.6RPA1, HELLS, DNASE1, DHX9
14alanine4410.6HELLS, FEN1, GYPA, POLB, DNASE1, LMNA
15mgcl24410.6DNASE1, HELLS
16dttp4410.6HELLS, POLB
17thymidylate4410.5POLB, HELLS, RPA1
18deoxyadenosine44 2411.5HELLS, DNASE1
19zinc44 2411.5LMNA, DNASE1, POLR1C, HELLS, RPA1
20polynucleotide4410.4POLB, WRN
21adenine44 11 2412.2HELLS, POLB, DNASE1

GO Terms for genes affiliated with Werner Syndrome

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16Gene Ontology
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Cellular components related to Werner Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1nucleusGO:00563410.5TERF2, RPA1, PURG, EXO1, HELLS, FEN1
2nucleoplasmGO:00565410.5RPA1, FEN1, WRN, POLR1C, POLB, RECQL5
3nuclear envelopeGO:00563510.5LMNA, DNASE1, TREX1
4nucleolusGO:00573010.4RPA1, FEN1, WRN, WRNIP1, BLM, RECQL
5lateral elementGO:00080010.4RPA1, BLM
6male germ cell nucleusGO:00167310.2BLM, RPA1

Biological processes related to Werner Syndrome according to GeneCards/GeneDecks:

(show all 20)
idNameGO IDScoreTop Affiliating Genes
1DNA recombinationGO:00631010.8RAD54L, RPA1, EXO1, WRN, TREX1, BLM
2DNA strand renaturationGO:00073310.8BLM, RECQL, RECQL4, RAD54L
3DNA repairGO:00628110.8RPA1, EXO1, FEN1, TREX1, POLB, BLM
4telomere maintenanceGO:00072310.8TERF2, BLM, WRN, FEN1, RPA1
5DNA replicationGO:00626010.8RPA1, FEN1, WRN, WRNIP1, TREX1, RECQL
6DNA duplex unwindingGO:03250810.8WRN, RECQL, RECQL4, RECQL5
7base-excision repairGO:00628410.8POLB, WRN, FEN1
8DNA metabolic processGO:00625910.7RECQL5, TREX1, WRN
9meiosisGO:00712610.7RPA1, EXO1, RAD54L
10double-strand break repair via homologous recombinationGO:00072410.7RAD54L, BLM, RPA1
11double-strand break repairGO:00630210.7WRN, FEN1, RPA1
12replication fork processingGO:03129710.7BLM, WRN
13positive regulation of type I interferon productionGO:03248110.7TREX1, POLR1C, DHX9
14ATP catabolic processGO:00620010.6BLM, WRNIP1, WRN
15DNA synthesis involved in DNA repairGO:00073110.6WRNIP1, WRN
16DNA-dependent DNA replicationGO:00626110.5RPA1, POLB
17mismatch repairGO:00629810.5TREX1, EXO1
18telomere maintenance via recombinationGO:00072210.5FEN1, RPA1
19nucleotide-excision repair, DNA gap fillingGO:00629710.4POLB, RPA1
20telomere maintenance via semi-conservative replicationGO:03220110.2FEN1, RPA1

Molecular functions related to Werner Syndrome according to GeneCards/GeneDecks:

(show all 17)
idNameGO IDScoreTop Affiliating Genes
1ATP-dependent 3-5 DNA helicase activityGO:04314010.8RECQL4, RECQL, BLM, WRN
2bubble DNA bindingGO:00040510.8WRN, BLM, RECQL4
3ATP-dependent DNA helicase activityGO:00400310.8DHX9, RECQL, BLM, WRN
4helicase activityGO:00438610.8RAD54L, BLM, WRN, HELLS
5exonuclease activityGO:00452710.7EXO1, FEN1, WRN
6four-way junction helicase activityGO:00937810.7BLM, WRN
7DNA bindingGO:00367710.7FEN1, HELLS, EXO1, PURG, WRN, WRNIP1
8ATP bindingGO:00552410.7HELLS, WRN, WRNIP1, BLM, RECQL, RECQL4
9DNA helicase activityGO:00367810.7RECQL5, RECQL, WRN
10G-quadruplex DNA bindingGO:05188010.6BLM, WRN
11protein bindingGO:00551510.6WRNIP1, WRN, FEN1, HELLS, EXO1, RPA1
12annealing helicase activityGO:03631010.6RAD54L, BLM
13single-stranded DNA bindingGO:00369710.5RPA1, TREX1, BLM
143-5 exonuclease activityGO:00840810.5TREX1, WRN
15ribonuclease H activityGO:00452310.5FEN1, EXO1
165-3 exonuclease activityGO:00840910.4FEN1, EXO1
17ATPase activityGO:01688710.2WRN, WRNIP1, BLM

Products for genes affiliated with Werner Syndrome

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Sources for Werner Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet