Details of Disease

Disease Name

Werner syndrome

WRN; Werner's syndrome; adult progeria; adult premature ageing syndrome; Werner syndrome; WS; adult premature aging syndrome

Definition

A rare inherited syndrome characterized by premature aging with onset in the third decade of life and with cardinal clinical features including bilateral cataracts, short stature, graying and thinning of scalp hair, characteristic skin disorders and premature onset of additional age-related disorders.

Disease Hierarchy

DIS6SVEE: Syndromic disease

DISCPWH9: Autosomal recessive disease

DISSLPEK: Progeroid syndrome

DISZY45W: Werner syndrome

Disease Identifiers

MONDO ID

MONDO_0010196

MESH ID

D014898

UMLS CUI

C0043119

OMIM ID

277700

MedGen ID

12147

Orphanet ID

902

SNOMED CT ID

51626007

General Information of Disease (ID: DISZY45W)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 41 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
WRN	OT81JS6K	Definitive	Autosomal recessive	[1]
EFEMP1	OTZVUOOB	Limited	Biomarker	[10]
GYPA	OTABU4YV	Limited	Genetic Variation	[11]
MRE11	OTGU8TZM	Limited	Biomarker	[12]
RECQL	OTPCH3JH	Limited	Genetic Variation	[13]
RECQL5	OTVZMP1Q	Limited	Biomarker	[14]
APLF	OTYUR3AH	moderate	Biomarker	[2]
CHD9	OTWNFDKJ	moderate	Biomarker	[15]
CKMT2	OT1KNPI1	moderate	Biomarker	[5]
DESI1	OTFNIW98	moderate	Biomarker	[16]
DHX9	OT5AAOQI	moderate	Biomarker	[17]
DNA2	OT4DJFFU	moderate	Biomarker	[7]
ENOSF1	OT65D3ZK	moderate	Biomarker	[18]
EXD3	OT2VQWK3	moderate	Biomarker	[19]
EXO1	OTI87RS5	moderate	Biomarker	[7]
GOLGA3	OT27354E	moderate	Biomarker	[20]
GTF2IRD2	OT63Q58O	moderate	Biomarker	[21]
HOXA3	OTIX5XFB	moderate	Biomarker	[5]
HOXA4	OTNVTQDT	moderate	Biomarker	[5]
HOXA6	OTHJP8M2	moderate	Biomarker	[5]
MBNL1	OTOV7J85	moderate	Biomarker	[22]
MON2	OTCSVMAR	moderate	Biomarker	[23]
NEIL1	OTHBU5DJ	moderate	Biomarker	[24]
PIWIL4	OTDA9MY0	moderate	Biomarker	[25]
POLL	OTZ24QGM	moderate	Biomarker	[26]
POU1F1	OTXT8A5C	moderate	Altered Expression	[8]
PPP2CB	OT24GMCM	moderate	Biomarker	[27]
PRPF19	OTQ1STV3	moderate	Biomarker	[28]
RAD54L	OTEGMAKG	moderate	Genetic Variation	[29]
RBPMS	OT1RDKR9	moderate	Genetic Variation	[30]
RPS3	OT0K3TMH	moderate	Biomarker	[31]
SLC35G1	OTKZUA8O	moderate	Biomarker	[16]
BLM	OTEJOAJX	Strong	Genetic Variation	[32]
DDX19A	OTBTDR44	Strong	Genetic Variation	[33]
DDX46	OTB2X9TO	Strong	Genetic Variation	[33]
DHX16	OTW8KZAU	Strong	Genetic Variation	[33]
FEN1	OT6QGG7O	Strong	Biomarker	[34]
HFM1	OTHV3EFE	Strong	Genetic Variation	[35]
RECQL4	OT59LSW7	Strong	Biomarker	[36]
SAMHD1	OTBCIBC7	Strong	Genetic Variation	[37]
TOP3A	OT3CKUI9	Strong	Biomarker	[38]
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⏷ Show the Full List of 41 DOT(s)

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
XRCC5	TTCB9KW	Limited	Biomarker	[2]
ANK1	TTKFPMH	moderate	Genetic Variation	[3]
BRIP1	TTZV7LJ	moderate	Biomarker	[4]
HOXA11	TTEX4ZA	moderate	Biomarker	[5]
HOXA7	TTMRE4Q	moderate	Biomarker	[5]
PLIN1	TTIV27N	moderate	Biomarker	[6]
RAD51	TTC0G1L	Strong	Altered Expression	[7]
WRN	TT2H5WQ	Definitive	Autosomal recessive	[1]
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⏷ Show the Full List of 8 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	moderate	Altered Expression	[8]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CES2	DETHCPD	moderate	Biomarker	[9]
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References

1	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2	Ligand binding characteristics of the Ku80 von Willebrand domain.DNA Repair (Amst). 2020 Jan;85:102739. doi: 10.1016/j.dnarep.2019.102739. Epub 2019 Oct 24.
3	Close linkage of the gene for Werner's syndrome to ANK1 and D8S87 on the short arm of chromosome 8.Gerontology. 1993;39 Suppl 1:11-5. doi: 10.1159/000213560.
4	Investigation of the core binding regions of human Werner syndrome and Fanconi anemia group J helicases on replication protein A.Sci Rep. 2019 Sep 30;9(1):14016. doi: 10.1038/s41598-019-50502-8.
5	Common and cell type-specific responses of human cells to mitochondrial dysfunction.Exp Cell Res. 2005 Jan 15;302(2):270-80. doi: 10.1016/j.yexcr.2004.09.006.
6	Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies.J Hum Genet. 2014 Jan;59(1):16-23. doi: 10.1038/jhg.2013.107. Epub 2013 Oct 24.
7	The Caenorhabditis elegans WRN helicase promotes double-strand DNA break repair by mediating end resection and checkpoint activation.FEBS Lett. 2017 Jul;591(14):2155-2166. doi: 10.1002/1873-3468.12724. Epub 2017 Jul 4.
8	Clinical outcome and mechanism of soft tissue calcification in Werner syndrome.Rejuvenation Res. 2008 Aug;11(4):809-19. doi: 10.1089/rej.2007.0649.
9	Effect of age and apoptosis on the mouse homologue of the huWRN gene.Mech Ageing Dev. 1998 Jun 1;103(1):27-44. doi: 10.1016/s0047-6374(98)00008-6.
10	Decrease of fibulin-3 in hepatocellular carcinoma indicates poor prognosis.PLoS One. 2013 Aug 1;8(8):e70511. doi: 10.1371/journal.pone.0070511. Print 2013.
11	Genetic instability and hematologic disease risk in Werner syndrome patients and heterozygotes.Cancer Res. 2000 May 1;60(9):2492-6.
12	Werner syndrome protein, the MRE11 complex and ATR: menage--trois in guarding genome stability during DNA replication?.Bioessays. 2004 Mar;26(3):306-13. doi: 10.1002/bies.10411.
13	Ectopic hTERT expression facilitates reprograming of fibroblasts derived from patients with Werner syndrome as a WS cellular model.Cell Death Dis. 2018 Sep 11;9(9):923. doi: 10.1038/s41419-018-0948-4.
14	RECQL5 plays co-operative and complementary roles with WRN syndrome helicase.Nucleic Acids Res. 2017 Feb 17;45(3):1566. doi: 10.1093/nar/gkw1216.
15	miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment.Mol Carcinog. 2018 Feb;57(2):295-302. doi: 10.1002/mc.22744. Epub 2017 Oct 31.
16	Molecular analysis of insulin receptor gene in Werner's syndrome.Diabetes Res Clin Pract. 1994 Dec 31;26(3):171-6. doi: 10.1016/0168-8227(94)90058-2.
17	Nuclear DNA helicase II (RNA helicase A) interacts with Werner syndrome helicase and stimulates its exonuclease activity.J Biol Chem. 2005 Sep 2;280(35):31303-13. doi: 10.1074/jbc.M503882200. Epub 2005 Jul 1.
18	Role of the Bloom's syndrome helicase in maintenance of genome stability.Biochem Soc Trans. 2001 May;29(Pt 2):201-4. doi: 10.1042/0300-5127:0290201.
19	Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD.Cell. 1999 Oct 15;99(2):133-41. doi: 10.1016/s0092-8674(00)81645-1.
20	Human cytomegalovirus UL97 kinase prevents the deposition of mutant protein aggregates in cellular models of Huntington's disease and ataxia.Neurobiol Dis. 2011 Jan;41(1):11-22. doi: 10.1016/j.nbd.2010.08.013. Epub 2010 Aug 20.
21	Cognitive, Behavioral, and Adaptive Profiles in Williams Syndrome With and Without Loss of GTF2IRD2.J Int Neuropsychol Soc. 2018 Oct;24(9):896-904. doi: 10.1017/S1355617718000711.
22	A 6.5mb deletion at 3q24q25.2 narrows Wisconsin syndrome critical region to a 750kb interval: A potential role for MBNLI.Am J Med Genet A. 2017 Jan;173(1):280-284. doi: 10.1002/ajmg.a.38002. Epub 2016 Oct 18.
23	DNA helicase activity in Werner's syndrome gene product synthesized in a baculovirus system.Nucleic Acids Res. 1997 Aug 1;25(15):2973-8. doi: 10.1093/nar/25.15.2973.
24	Werner syndrome (WRN) DNA helicase and base excision repair (BER) factors maintain endothelial homeostasis.DNA Repair (Amst). 2019 Jan;73:17-27. doi: 10.1016/j.dnarep.2018.10.005. Epub 2018 Oct 28.
25	Roles of RNase P and Its Subunits.Trends Genet. 2017 Sep;33(9):594-603. doi: 10.1016/j.tig.2017.06.006. Epub 2017 Jul 8.
26	Mutations induced by 8-oxo-7,8-dihydroguanine in WRN- and DNA polymerase -double knockdown cells.Mutagenesis. 2018 Oct 11;33(4):301-310. doi: 10.1093/mutage/gey024.
27	A 2.8 megabase YAC contig spanning D8S339, which is tightly linked to the Werner syndrome locus.Genome. 1997 Feb;40(1):77-83. doi: 10.1139/g97-010.
28	The Pso4 mRNA splicing and DNA repair complex interacts with WRN for processing of DNA interstrand cross-links.J Biol Chem. 2005 Dec 9;280(49):40559-67. doi: 10.1074/jbc.M508453200. Epub 2005 Oct 12.
29	hRAD54 gene and 1p high-resolution deletion-mapping analyses in oligodendrogliomas.Cancer Genet Cytogenet. 2000 Jan 15;116(2):142-7. doi: 10.1016/s0165-4608(99)00122-3.
30	A unique human gene that spans over 230 kb in the human chromosome 8p11-12 and codes multiple family proteins sharing RNA-binding motifs.Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10913-7. doi: 10.1073/pnas.93.20.10913.
31	Proteome-wide identification of WRN-interacting proteins in untreated and nuclease-treated samples.J Proteome Res. 2011 Mar 4;10(3):1216-27. doi: 10.1021/pr100990s. Epub 2011 Feb 16.
32	Functional conservation of RecQ helicase BLM between humans and Drosophila melanogaster.Sci Rep. 2019 Nov 26;9(1):17527. doi: 10.1038/s41598-019-54101-5.
33	Werner's syndrome: from clinics to genetics.Clin Exp Rheumatol. 2000 Nov-Dec;18(6):760-6.
34	The Werner Syndrome Helicase Coordinates Sequential Strand Displacement and FEN1-Mediated Flap Cleavage during Polymerase Elongation.Mol Cell Biol. 2017 Jan 19;37(3):e00560-16. doi: 10.1128/MCB.00560-16. Print 2017 Feb 1.
35	RECQ helicase disease and related progeroid syndromes: RECQ2018 meeting.Mech Ageing Dev. 2018 Jul;173:80-83. doi: 10.1016/j.mad.2018.05.002. Epub 2018 May 9.
36	Bloom's syndrome: Why not premature aging?: A comparison of the BLM and WRN helicases.Ageing Res Rev. 2017 Jan;33:36-51. doi: 10.1016/j.arr.2016.05.010. Epub 2016 May 26.
37	Atypical Aicardi-Goutieres syndrome: is the WRN locus a modifier?.Am J Med Genet A. 2014 Oct;164A(10):2510-3. doi: 10.1002/ajmg.a.36664. Epub 2014 Jul 2.
38	WRN helicase defective in the premature aging disorder Werner syndrome genetically interacts with topoisomerase 3 and restores the top3 slow growth phenotype of sgs1 top3.Aging (Albany NY). 2009 Feb 5;1(2):219-33. doi: 10.18632/aging.100020.