Raras
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Síndrome Werner
ORPHA:902CID-10 · E34.8CID-11 · LD2BOMIM 277700DOENÇA RARA

É uma síndrome hereditária rara caracterizada por um envelhecimento precoce, que geralmente começa entre os 20 e 30 anos de idade. Os principais sinais e sintomas incluem: catarata nos dois olhos, baixa estatura, cabelos do couro cabeludo que ficam grisalhos e mais finos, problemas de pele característicos e o surgimento adiantado de outras doenças relacionadas à idade.

Mantido por Agente Raras·Colaborar como especialista →

Introdução

O que você precisa saber de cara

📋

É uma síndrome hereditária rara caracterizada por um envelhecimento precoce, que geralmente começa entre os 20 e 30 anos de idade. Os principais sinais e sintomas incluem: catarata nos dois olhos, baixa estatura, cabelos do couro cabeludo que ficam grisalhos e mais finos, problemas de pele característicos e o surgimento adiantado de outras doenças relacionadas à idade.

Pesquisas ativas
1 ensaio
7 total registrados no ClinicalTrials.gov
Publicações científicas
1.228 artigos
Último publicado: 2026 Mar 31

Escala de raridade

CLASSIFICAÇÃO ORPHANET · BRASIL 2024
1-9 / 1 000 000
Ultra-rara
<1/50k
Muito rara
1/20k
Rara
1/10k
Pouco freq.
1/5k
Incomum
1/2k
Prevalência
0.5
Europe
Início
Adolescent
+ adult
🏥
SUS: Sem cobertura SUSScore: 0%
CID-10: E34.8
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Entender a doença

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Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

🧬
Pele e cabelo
12 sintomas
🦴
Ossos e articulações
7 sintomas
📏
Crescimento
6 sintomas
👁️
Olhos
3 sintomas
💪
Músculos
3 sintomas
😀
Face
3 sintomas

+ 40 sintomas em outras categorias

Características mais comuns

100%prev.
Início juvenil
Obrigatório (100%)
100%prev.
Anomalia do desenvolvimento do giro frontal inferior
Obrigatório (100%)
100%prev.
Dor lombar
Obrigatório (100%)
100%prev.
Hipertrigliceridemia
Frequência: 2/2
100%prev.
Diabetes mellitus
Frequência: 2/2
100%prev.
Hiperglicemia
Frequência: 2/2
84sintomas
Muito frequente (38)
Frequente (24)
Ocasional (20)
Sem dados (2)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 84 características clínicas mais associadas, ordenadas por frequência.

Início juvenilJuvenile onset
Obrigatório (100%)100%
Anomalia do desenvolvimento do giro frontal inferiorHP:0011462
Obrigatório (100%)100%
Dor lombarLow back pain
Obrigatório (100%)100%
HipertrigliceridemiaHypertriglyceridemia
Frequência: 2/2100%
Diabetes mellitus
Frequência: 2/2100%

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa1desde 2026
Total histórico1.228PubMed
Últimos 10 anos200publicações
Pico202552 papers
Linha do tempo
2026Hoje · 2026🧪 1992Primeiro ensaio clínico📈 2025Ano de pico
Publicações por ano (últimos 10 anos)

Encontrou um erro ou informação desatualizada? Sugira uma correção →

Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

1 gene identificado com associação a esta condição. Padrão de herança: Autosomal recessive.

WRNBifunctional 3'-5' exonuclease/ATP-dependent helicase WRNDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Multifunctional enzyme that has magnesium and ATP-dependent 3'-5' DNA-helicase activity on partially duplex substrates (PubMed:9224595, PubMed:9288107, PubMed:9611231). Also has 3'->5' exonuclease activity towards double-stranded (ds)DNA with a 5'-overhang (PubMed:11863428). Has no nuclease activity towards single-stranded (ss)DNA or blunt-ended dsDNA (PubMed:11863428). Helicase activity is most efficient with (d)ATP, but (d)CTP will substitute with reduced efficiency; strand displacement is enh

LOCALIZAÇÃO

Nucleus, nucleolusNucleusNucleus, nucleoplasmChromosome

VIAS BIOLÓGICAS (10)
Regulation of TP53 Activity through PhosphorylationG2/M DNA damage checkpointProcessing of DNA double-strand break endsPresynaptic phase of homologous DNA pairing and strand exchangeHDR through Single Strand Annealing (SSA)
MECANISMO DE DOENÇA

Werner syndrome

A rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction.

EXPRESSÃO TECIDUAL(Ubíquo)
Linfócitos
19.4 TPM
Fibroblastos
17.0 TPM
Útero
15.8 TPM
Ovário
11.8 TPM
Nervo tibial
11.7 TPM
OUTRAS DOENÇAS (1)
Werner syndrome
HGNC:12791UniProt:Q14191

Variantes genéticas (ClinVar)

574 variantes patogênicas registradas no ClinVar.

🧬 WRN: NM_000553.6(WRN):c.2631-2A>G ()
🧬 WRN: NM_000553.6(WRN):c.1349_1350+9del ()
🧬 WRN: NM_000553.6(WRN):c.1269+2T>C ()
🧬 WRN: NM_000553.6(WRN):c.3349A>T (p.Lys1117Ter) ()
🧬 WRN: NM_000553.6(WRN):c.1720+1G>A ()
Ver todas no ClinVar

Classificação de variantes (ClinVar)

Distribuição de 3,734 variantes classificadas pelo ClinVar.

373
1867
1494
Patogênica (10.0%)
VUS (50.0%)
Benigna (40.0%)
VARIANTES MAIS SIGNIFICATIVAS
WRN: NM_000553.6(WRN):c.2631-2A>G [Likely pathogenic]
WRN: NM_000553.6(WRN):c.1349_1350+9del [Likely pathogenic]
WRN: NM_000553.6(WRN):c.3983-9C>A [Uncertain significance]
LOC126860342: NM_000553.6(WRN):c.4243A>C (p.Ser1415Arg) [Uncertain significance]
WRN: NM_000553.6(WRN):c.3384-5T>C [Uncertain significance]

Diagnóstico

Os sinais que médicos procuram e os exames que confirmam

Carregando...

Tratamento e manejo

Remédios, cuidados de apoio e o que precisa acompanhar

Pipeline de tratamentos
Pipeline regulatório — de medicamentos já aprovados a drogas em pesquisa exploratória.
2Fase 21
1Fase 11
·Pré-clínico1
Medicamentos catalogadosEnsaios clínicos· 0 medicamentos · 3 ensaios
Carregando informações de tratamento...

Onde tratar no SUS

Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)

🇧🇷 Atendimento SUS — Síndrome Werner

🗺️

Selecione um estado ou use sua localização para ver resultados.

Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.

Pesquisa ativa

Ensaios clínicos abertos e novidades científicas recentes

Pesquisa e ensaios clínicos

7 ensaios clínicos encontrados, 1 ativos.

Distribuição por fase
Ver todos no ClinicalTrials.gov
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Publicações mais relevantes

Timeline de publicações
390 papers (10 anos)
#1

Deficiency of Werner RecQ-type DNA helicase causes premature malnutrition in zebrafish.

iScience2026 Mar 20

Werner syndrome is a genetic progeria characterized by premature aging symptoms, but its early-onset pathology remains unclear. We generated wrn truncation mutant (wrn -/-) zebrafish using CRISPR/Cas9 and identified two premature mortality phases: 7-21 and 60-90 days post-fertilization (dpf). Time-course transcriptomics revealed two wrn -/- subgroups. One showed the reduced expression of intestinal and pancreatic exocrine genes at 7-9 dpf, while the other maintained normal expression initially but eventually showed reduced pancreatic exocrine genes by 21-35 dpf. The prematurely dying wrn -/- larvae exhibited intestinal villi and pancreatic defects, along with DNA damage, cell-cycle arrest, and apoptosis. They also had lower glycogen, glucose, and fat levels compared to wild-type and late-dying wrn -/- larvae, suggesting malnutrition. Notably, excess feeding partially improved their survival. These findings reveal early pathological features in the zebrafish model of Werner syndrome.

#2

Unraveling syndrome-driven osteosarcoma: genetic insights and therapeutic frontiers.

Orphanet journal of rare diseases2026 Feb 06

Osteosarcoma is a highly malignant bone tumor, and a subset of cases is closely associated with hereditary syndromes. These syndrome-related osteosarcomas exhibit unique clinical features, molecular mechanisms, and therapeutic challenges. This review summarizes the current understanding of specific types of syndrome-related osteosarcomas, including those associated with Rothmund-Thomson syndrome, Li-Fraumeni syndrome, secondary osteosarcoma in retinoblastoma survivors, Werner syndrome, and Bloom syndrome. These syndromes are typically characterized by specific gene mutations or chromosomal instability, significantly increasing the risk of osteosarcoma development. However, the rarity and heterogeneity of syndrome-related osteosarcomas pose significant challenges for diagnosis and treatment, including difficulties in early detection, incomplete elucidation of molecular mechanisms, and limitations of conventional therapeutic approaches. This article aims to systematically review the clinical characteristics, molecular mechanisms, and therapeutic challenges of these syndromes, providing a comprehensive reference for clinicians and directions for future research.

#3

Novel Homozygous Variants in CIDEC and WRN in a Young Female with Lipodystrophy and Thyroid Cancer.

International journal of molecular sciences2026 Jan 08

Autosomal recessive familial partial lipodystrophy type 5 (FPLD5) due to a homozygous NP_001186481.1; p.E186* CIDEC variant has previously been reported in a 19-year-old female with diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. Now, we report an 18-year-old Hispanic female who presented with FPL, along with hirsutism, acanthosis nigricans, and marked insulin resistance, and was found to have an extremely rare homozygous variant in CIDEC (NM_001199623.2:c.224G>T; NP_001186552.1; p.Ser75Ile) by whole exome sequencing. She also harbored a novel homozygous variant in WRN (NM_000553.4:c.1856T>G; NP_000544; p.Leu619Arg). Both serine 75 of the CIDEC protein and leucine 619 of the WRN protein were well conserved across species. She developed an invasive papillary thyroid carcinoma at the age of 17 years. Our report confirms the previously reported association of the biallelic CIDEC variant with the FPL phenotype and also highlights the extremely rare possibility of co-occurrence of FPLD5 with thyroid cancer, a clinical feature of Werner syndrome. Thus, our patient may not only need surveillance for the metabolic complications of FPLD5, such as diabetes, hypertriglyceridemia, and hepatic steatosis, but also for WRN-associated neoplasms and features of premature aging.

#4

WRN structural flexibility showcased through fragment-based lead discovery of inhibitors.

Nature communications2026 Jan 03

WRN helicase is an established synthetic lethal target for inhibition in the treatment of microsatellite instability-high (MSI-H) and mismatch repair deficient (MMRd) cancers. The identification of helicase inhibitors is challenging as high-throughput biochemical screening campaigns typically return few validated hits that are often inactive in cell-based assays. Herein, we highlight the power of non-covalent fragment-based lead discovery in locating new druggable allosteric sites on WRN, enabling us to bypass the challenging behavior of WRN during high-throughput screening hampering hit identification. During the fragment optimization process, structures of WRN with key prioritized fragments reveal multiple conformations of WRN with significant domain rotations up to 180°, including a WRN conformation not previously described. Rooted in a combination of biochemical, biophysical, and structural approaches, we present the detailed analyses of optimized chemical matter evolved from screening hits and the unique ability of WRN to accommodate diverse conformations as detailed by structural characterization.

#5

Prognostic Significance of DNA Repair Gene mRNA Expression in Early-Stage Breast Cancer: Insights into Clinical Relevance.

Oncology research2026

The prognostic and therapeutic roles of biological markers in early-stage breast cancer (eBC) warrant further investigation. Non-Breast Cancer (BRCA) genes, along with moderate- and low-penetrance breast cancer risk variant genes, are crucial for maintaining genome stability, yet their prognostic significance in eBC remains unclear. This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients. Significant correlations were observed between the messenger ribonucleic acid (mRNA) expression levels of the genes Ataxia-telangiectasia mutated (ATM), Bloom helicase gene (BLM), and WRN RecQ Like Helicase (WRN) and patient prognosis. High mRNA expression of ATM was associated with longer metastasis-free survival (MFS). Conversely, lower mRNA expression of BLM correlated with favorable outcomes, particularly in triple-negative tumors. Additionally, high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels. This study highlights the prognostic significance of ATM, BLM, and WRN in predicting survival outcomes in eBC patients. The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer (eBC) remains unclear and warrants further investigation. This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer. Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid (mRNA) expression levels. Statistical analysis, including Kaplan-Meier curves, univariable, and multivariable Cox regression analyses, was performed to assess metastasis-free survival (MFS) of mRNA expression of non-BRCA genes. Subgroup analyses were also conducted among four different molecular subtypes of eBC. Our analysis revealed significant correlations between mRNA-expression levels of Ataxia-telangiectasia mutated (ATM), Bloom helicase gene (BLM), and WRN RecQ Like Helicase (WRN) and patient prognosis. High mRNA expression of ATM correlated with longer MFS in the entire cohort (p = 0.022, Log Rank), and in luminal-B-like tumors (p = 0.036). Lower mRNA expression of BLM was associated with favorable outcomes (p = 0.011, Log Rank), particularly in triple-negative eBC (p = 0.030, Log Rank). Finally, high levels of WRN mRNA expression correlated with significantly longer MFS compared to low mRNA expression levels (p = 0.009, Log Rank). This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes, such as ATM, BLM, and WRN, for survival outcomes in eBC.

Publicações recentes

Ver todas no PubMed

📚 EuropePMC680 artigos no totalmostrando 198

2026

Prognostic Significance of DNA Repair Gene mRNA Expression in Early-Stage Breast Cancer: Insights into Clinical Relevance.

Oncology research
2026

Deficiency of Werner RecQ-type DNA helicase causes premature malnutrition in zebrafish.

iScience
2026

Discovery and Preclinical Evaluations of Potent, Selective, and Allosteric Covalent WRN Inhibitors with Improved PK Properties.

ACS medicinal chemistry letters
2026

Novel Werner Syndrome RecQ DNA Helicase (WRN) Inhibitors for Cancer Treatment.

ACS medicinal chemistry letters
2026

Microsatellite instable cancer cells acquire on-target resistance mutations to WRN helicase inhibitors.

Molecular cancer therapeutics
2026

Unraveling syndrome-driven osteosarcoma: genetic insights and therapeutic frontiers.

Orphanet journal of rare diseases
2026

Structural insights into WRN helicase reveal conformational states and opportunities for MSI-H cancer drug discovery.

Communications biology
2026

Novel Homozygous Variants in CIDEC and WRN in a Young Female with Lipodystrophy and Thyroid Cancer.

International journal of molecular sciences
2026

The Werner syndrome RECQ helicase as a therapeutic target: new insights.

Expert opinion on therapeutic targets
2026

WRN structural flexibility showcased through fragment-based lead discovery of inhibitors.

Nature communications
2025

Tumorigenic p53N236S balances aging and tumorigenesis via regulating DREAM/MMB and downstream telomere DNA replication pathways.

Journal of molecular cell biology
2026

Efficacy and safety of SGLT2 inhibitor on insulin resistance and hyperglycemia in Werner syndrome-A case report.

Journal of diabetes investigation
2025

Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.

Targeted oncology
2025

The Relationship Between Insulin Resistance and Cancer in Humans.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
2026

The bacterial MRE11-RAD50 and DNA2-WRN homologs process replication forks at distinct and separate loci on the chromosome.

FEBS letters
2025

DNA repair helicases: from mechanistic understanding to therapeutic implications.

NAR cancer
2026

AI-assisted delivery of novel covalent WRN inhibitors from a non-covalent fragment screen.

Bioorganic &amp; medicinal chemistry letters
2025

Editor's Note: Werner Syndrome Helicase Has a Critical Role in DNA Damage Responses in the Absence of a Functional Fanconi Anemia Pathway.

Cancer research
2025

Molecular Mechanisms of Proliferative Senescence and Genomic Instability in Werner Syndrome and the WRN Gene Network.

Cytogenetic and genome research
2025

Identification of VVD-214/RO7589831, a Clinical-Stage, Covalent Allosteric Inhibitor of WRN Helicase for the Treatment of MSI-High Cancers.

Journal of medicinal chemistry
2025

Targeted degradation of Werner syndrome helicase (WRN) via ligand-directed covalent hydrophobic tagging.

European journal of medicinal chemistry
2025

WRN and WRNIP1 ATPases impose high fidelity on translesion synthesis by Y-family DNA polymerases.

eLife
2025

High-throughput evaluation of novel WRN inhibitors.

SLAS discovery : advancing life sciences R &amp; D
2025

DNA double-strand break end resection factors and WRN facilitate mitotic DNA synthesis in human cells.

Nature communications
2025

Targeting the Werner syndrome protein in microsatellite instability cancers: mechanisms and therapeutic potential.

Clinical and experimental medicine
2025

A case of rapid-progressing liver cirrhosis complicated by Werner syndrome.

Clinical journal of gastroenterology
2025

An overview of RecQ helicases and related diseases.

Aging
2025

Targeting WRN helicase: Discovery and development of its selective inhibitors.

Bioorganic chemistry
2025

Werner syndrome due to homozygous WRN mutation through chromosome 8 region of homozygosity in a consanguineous family.

Geriatrics &amp; gerontology international
2025

Quinazoline Derivative kzl052 Suppresses Prostate Cancer by Targeting WRN Helicase to Stabilize DNA Replication Forks.

International journal of molecular sciences
2025

Thioguanine-coordinated assembly for synthetic lethality of colorectal cancer with defective mismatch repair.

Chemical communications (Cambridge, England)
2025

Post-Translational Modifications of the Werner Syndrome Protein WRN.

Cytogenetic and genome research
2025

Whole Exome Sequencing Identifies a Novel Frameshift Mutation of the WRN Gene in a Werner Syndrome Family and Functional Analysis.

Molecular genetics &amp; genomic medicine
2025

Synthetic Lethality as Emerging Treatment for Cancer: An Example by Using the Werner Syndrome Helicase (WRN) Inhibitors.

ACS medicinal chemistry letters
2025

Targeting Werner Syndrome Helicase with Small Molecules in Mismatch Repair-Deficient Cancers.

ACS medicinal chemistry letters
2025

WRN as a Novel Target of Synthetic Lethality: Current Advances and Future Perspectives.

Journal of medicinal chemistry
2026

Design and synthesis of 2-amino-4-(trifluoromethyl)pyrimidine derivatives as potential Werner-dependent antiproliferative agents.

Molecular diversity
2025

Targeting Werner Helicase: A novel combination strategy for MSI colorectal cancer.

Biochemical pharmacology
2025

Validation, Key Pharmacophores, and X-ray Cocrystal Structures of Novel Biochemically and Cellularly Active WRN Inhibitors Derived from a DNA-Encoded Library Screen.

Journal of medicinal chemistry
2025

Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial.

Aging cell
2025

Investigating telomere length in progeroid syndromes: implications for aging disorders.

Aging
2025

CEBPA-associated familial acute myeloid leukemia mimicking Werner syndrome: a case report.

Frontiers in genetics
2025

Werner syndrome exonuclease promotes gut regeneration and causes age-associated gut hyperplasia in Drosophila.

PLoS biology
2025

A Rare Cause of Acute Pancreatitis: Two Siblings With Werner Syndrome.

JCEM case reports
2025

Werner helicase as a therapeutic target in mismatch repair deficient colorectal cancer.

DNA repair
2025

Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation.

Aging
2025

Crystal-storing histiocytosis of multiple myeloma with a novel multi-exon deletion of WRN: A case report and mini review of literature.

Pathology, research and practice
2026

Discovery of novel quinazoline derivatives containing trifluoromethyl against cell proliferation by targeting werner helicase.

Molecular diversity
2025

PLK1 phosphorylates WRN at replication forks.

The Journal of pharmacology and experimental therapeutics
2025

Extrachromosomal circular DNA: a double-edged sword in cancer progression and age-related diseases.

Human cell
2025

A Rare Presentation of Five Primary Cancers in a Patient With Werner Syndrome: A Case Report and Literature Review.

Cureus
2025

Discovery of novel WRN inhibitors for treating MSI-H colorectal cancers.

Bioorganic &amp; medicinal chemistry letters
2025

Genetic and Epigenetic Insights into Werner Syndrome.

Cytogenetic and genome research
2025

Long-term follow-up of a case of bilateral elbow ulcers in a patient with Werner syndrome treated with pedicled radial forearm flaps.

Case reports in plastic surgery &amp; hand surgery
2025

For early diagnosis of young patients with Werner syndrome: Indication for genetic testing.

Geriatrics &amp; gerontology international
2025

Establishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug.

Proceedings of the National Academy of Sciences of the United States of America
2025

Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.

Nature communications
2025

Amelioration of premature aging in Werner syndrome stem cells by targeting SHIP/AKT pathway.

Cell &amp; bioscience
2025

A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.

Cancers
2025

rDNA Copy Number Variation and Methylation During Normal and Premature Aging.

Aging cell
2025

Synergistic protection of nascent DNA at stalled forks by MSANTD4 and BRCA1/2-RAD51.

Nature chemical biology
2025

Efficacy of eribulin monotherapy for bone marrow carcinomatosis of breast cancer in a patient with Werner syndrome.

Geriatrics &amp; gerontology international
2025

Specific Monitoring the DNA Helicase Function via Anchor-Embedded DNA Probe.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
2024

Application and research progress of synthetic lethality in the development of anticancer therapeutic drugs.

Frontiers in oncology
2024

Less frequent skin ulcers among patients with Werner syndrome treated with pioglitazone: findings from the Japanese Werner Syndrome Registry.

Aging
2024

Quinazoline derivatives inhibit cell growth of prostate cancer as a WRN helicase dependent manner by regulating DNA damage repair and microsatellite instability.

Bioorganic chemistry
2025

Design, synthesis, and structure-activity relationship studies of triazolo-pyrimidine derivatives as WRN inhibitors for the treatment of MSI tumors.

European journal of medicinal chemistry
2024

Werner syndrome RECQ helicase participates in and directs maintenance of the protein complexes of constitutive heterochromatin in proliferating human cells.

Aging
2024

p21 Regulates Wnt-Notch balance via DREAM/MMB/Rb-E2F1 and maintains intestinal stem cell homeostasis.

Cell death discovery
2024

Switch-like phosphorylation of WRN integrates end-resection with RAD51 metabolism at collapsed replication forks.

Nucleic acids research
2024

Peri-operative considerations for a pregnant patient with Werner syndrome and pre-eclampsia.

Anaesthesia reports
2024

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.

Nature communications
2024

Interdependence between Nuclear Pore Gatekeepers and Genome Caretakers: Cues from Genome Instability Syndromes.

International journal of molecular sciences
2024

Promotion of DNA end resection by BRCA1-BARD1 in homologous recombination.

Nature
2024

Mechanism of BRCA1-BARD1 function in DNA end resection and DNA protection.

Nature
2024

PROTAC-mediated conditional degradation of the WRN helicase as a potential strategy for selective killing of cancer cells with microsatellite instability.

Scientific reports
2024

WRN Nuclease-Mediated EcDNA Clearance Enhances Antitumor Therapy in Conjunction with Trehalose Dimycolate/Mesoporous Silica Nanoparticles.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
2024

Recommendations for cancer screening and surveillance in patients with Werner syndrome.

Geriatrics &amp; gerontology international
2024

SNORD88B-mediated WRN nucleolar trafficking drives self-renewal in liver cancer initiating cells and hepatocarcinogenesis.

Nature communications
2024

WRN Helicase: Is There More to MSI-H than Immunotherapy?

Cancer discovery
2024

WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis.

Nature communications
2024

James German and the Quest to Understand Human RECQ Helicase Deficiencies.

Cells
2024

High-Throughput Covalent Modifier Screening with Acoustic Ejection Mass Spectrometry.

Journal of the American Chemical Society
2024

Genomic and Transcriptomic Analysis of a Patient with Early-Onset Colorectal Cancer and Therapy-Induced Focal Nodular Hyperplasia: A Case Report.

Journal of personalized medicine
2024

'Werner Syndrome foot'-A case series of four Irish Traveller siblings with Werner Syndrome, diabetes mellitus and complex foot disease.

Diabetic medicine : a journal of the British Diabetic Association
2024

KBM-mediated interactions with KU80 promote cellular resistance to DNA replication stress in CHO cells.

DNA repair
2024

RecQ helicase expression in patients with telomeropathies.

Molecular biology reports
2024

Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model.

Nature communications
2024

Integrated liver and serum proteomics uncover sexual dimorphism and alteration of several immune response proteins in an aging Werner syndrome mouse model.

Aging
2025

Development of a Prognostic Risk Model Based on Oxidative Stress-related Genes for Platinum-resistant Ovarian Cancer Patients.

Recent patents on anti-cancer drug discovery
2025

Design and synthesis of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential Werner-dependent antiproliferative agents.

Molecular diversity
2024

WRN inhibitors squeeze cancer cell vulnerability.

Nature reviews. Drug discovery
2024

Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers.

Nature
2024

Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase.

Nature
2024

DNA repair deficiencies and neurodegeneration.

DNA repair
2024

Werner Syndrome and Diabetes: Opportunities for Precision Medicine.

Diabetes care
2024

Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells.

Cancer discovery
2024

Targeting ATP-binding site of WRN Helicase: Identification of novel inhibitors through pocket analysis and Molecular Dynamics-Enhanced virtual screening.

Bioorganic &amp; medicinal chemistry letters
2024

Discovering potential WRN inhibitors from natural product database through computational methods.

Journal of molecular graphics &amp; modelling
2024

WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases.

Genes &amp; development
2024

Dietary restriction fails to extend lifespan of Drosophila model of Werner syndrome.

G3 (Bethesda, Md.)
2023

Premature aging in genetic diseases: what conclusions can be drawn for physiological aging.

Frontiers in aging
2023

Breast cancer in a Hispanic patient with Werner syndrome.

Journal of radiology case reports
2024

Challenges for the Discovery of Non-Covalent WRN Helicase Inhibitors.

ChemMedChem
2024

Discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for treating cancers with microsatellite instability.

Bioorganic &amp; medicinal chemistry
2024

A Novel Variant in the WRN Gene Detected in a Case of Early-Onset Severe Insulin Resistance Displaying Some but Not All Hallmarks of Progeroid Werner Syndrome.

Diabetes care
2024

WRN loss accelerates abnormal adipocyte metabolism in Werner syndrome.

Cell &amp; bioscience
2024

CRL2APPBP2-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence.

Science China. Life sciences
2024

The function of Bazhen decoction in rescuing progeroid cell senescence via facilitating G-quadruplex resolving and telomere elongation.

Journal of ethnopharmacology
2024

Werner Syndrome Caused by Homozygous Frameshift Variant c.1578del in WRN.

Acta medica Lituanica
2023

Sclerosing epithelioid fibrosarcoma associated with WRN gene variant presenting as chronic dyspnea and pathologic cervical fracture: a case report and review of the literature.

Journal of medical case reports
2024

The dual role of the DREAM/G2M pathway in non-tumorigenic immortalization of senescent cells.

FEBS open bio
2024

Sex differences in symptom presentation and their impact on diagnostic accuracy in Werner syndrome.

Geriatrics &amp; gerontology international
2024

Case of Werner syndrome complicated with Sjögren's syndrome and Hashimoto's thyroiditis presenting sclerosing panniculitis-like symptoms.

Geriatrics &amp; gerontology international
2024

Werner helicase mediates the senescence and cell cycle of leukemia cells by regulating DNA repair pathways.

International journal of biological macromolecules
2023

WRN Is a Promising Synthetic Lethal Target for Cancers with Microsatellite Instability (MSI).

Cancer treatment and research
2023

Comprehensive mapping of cell fates in microsatellite unstable cancer cells supports dual targeting of WRN and ATR.

Genes &amp; development
2023

Flame-like Calcifications in Werner Syndrome.

JCEM case reports
2024

The identification of a novel mutation (p.I223fs) in WRN associated with Werner syndrome.

Endocrine
2023

Modified iPOND revealed the role of mutant p53 in promoting helicase function and telomere maintenance.

Aging
2024

Early-onset diabetes mellitus as a presenting feature of Werner's syndrome in an Indian family.

Molecular genetics &amp; genomic medicine
2023

Senescence-associated inflammation and inhibition of adipogenesis in subcutaneous fat in Werner syndrome.

Aging
2024

Senescence, regulators of alternative splicing and effects of trametinib treatment in progeroid syndromes.

GeroScience
2023

PHOSPHORYLATION-DEPENDENT ASSOCIATION OF WRN WITH RPA IS REQUIRED FOR RECOVERY OF REPLICATION FORKS STALLED AT SECONDARY DNA STRUCTURES.

bioRxiv : the preprint server for biology
2023

ssDNA reeling is an intermediate step in the reiterative DNA unwinding activity of the WRN-1 helicase.

The Journal of biological chemistry
2023

Brain and/or Spinal Cord Tumors Accompanied with Other Diseases or Syndromes.

Advances in experimental medicine and biology
2023

Werner syndrome associated with poorly differentiated thyroid carcinoma and systemic sclerosis-like skin manifestations: A case report.

Modern rheumatology case reports
2023

Identification of 2-Sulfonyl/Sulfonamide Pyrimidines as Covalent Inhibitors of WRN Using a Multiplexed High-Throughput Screening Assay.

Biochemistry
2023

Cancer aneuploidies are shaped primarily by effects on tumour fitness.

Nature
2023

Werner syndrome as a crossroads between lipodystrophy, escleroderma-like changes and torpid ulcers in lower limbs.

Endocrinologia, diabetes y nutricion
2023

A rapid and highly sensitive immunosorbent assay to monitor helicases unwinding diverse nucleic acid structures.

The Analyst
2023

Renal dysfunction, malignant neoplasms, atherosclerotic cardiovascular diseases, and sarcopenia as key outcomes observed in a three-year follow-up study using the Werner Syndrome Registry.

Aging
2023

RecQ dysfunction contributes to social and depressive-like behavior and affects aldolase activity in mice.

Neurobiology of disease
2023

Identification of Novel Senescent Markers in Small Extracellular Vesicles.

International journal of molecular sciences
2023

Case of Werner syndrome with significant improvement of refractory skin ulcer despite fibroblast cellular senescence.

Geriatrics &amp; gerontology international
2023

Quality of life in Werner syndrome and associated subjective foot/ankle symptoms: A cross-sectional survey.

Geriatrics &amp; gerontology international
2023

Combination of untargeted and targeted proteomics for secretome analysis of L-WRN cells.

Analytical and bioanalytical chemistry
2023

A non-catalytic N-terminus domain of WRN prevents mitotic telomere deprotection.

Scientific reports
2023

WRN suppresses p53/PUMA-induced apoptosis in colorectal cancer with microsatellite instability/mismatch repair deficiency.

Proceedings of the National Academy of Sciences of the United States of America
2022

Targeting G-quadruplex for rescuing impaired chondrogenesis in WRN-deficient stem cells.

Cell &amp; bioscience
2023

Werner syndrome protein works as a dimer for unwinding and replication fork regression.

Nucleic acids research
2022

RNaseH2A downregulation drives inflammatory gene expression via genomic DNA fragmentation in senescent and cancer cells.

Communications biology
2023

WRN helicase and mismatch repair complexes independently and synergistically disrupt cruciform DNA structures.

The EMBO journal
2023

Werner helicase is required for proliferation and DNA damage repair in multiple myeloma.

Molecular biology reports
2022

Synthetical lethality of Werner helicase and mismatch repair deficiency is mediated by p53 and PUMA in colon cancer.

Proceedings of the National Academy of Sciences of the United States of America
2022

Optical coherence tomography findings in three patients with Werner syndrome.

BMC ophthalmology
2022

Adult progeria: a new mutation in the WRN gene.

BMJ case reports
2022

Biochemical and functional characterization of an exonuclease from Chaetomium thermophilum.

Biochemical and biophysical research communications
2022

Research on Werner Syndrome: Trends from Past to Present and Future Prospects.

Genes
2022

Werner syndrome associated with acroosteolysis.

Dermatology online journal
2023

A homozygous missense variant in the WRN gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease.

American journal of medical genetics. Part A
2022

Literature-based translation from synthetic lethality screening into therapeutics targets: CD82 is a novel target for KRAS mutation in colon cancer.

Computational and structural biotechnology journal
2023

A rare syndrome mimicking scleroderma: Werner syndrome.

Modern rheumatology case reports
2023

Peripheral neuropathies associated with DNA repair disorders.

Muscle &amp; nerve
2022

WRN promotes bone development and growth by unwinding SHOX-G-quadruplexes via its helicase activity in Werner Syndrome.

Nature communications
2022

DNA fiber analyses to study functional importance of helicases and associated factors during replication stress.

Methods in enzymology
2022

Case Report: A novel WRN mutation in Werner syndrome patient with diabetic foot disease and myelodysplastic syndrome.

Frontiers in endocrinology
2022

Partial lipodystrophy, severe dyslipidaemia and insulin resistant diabetes as early signs of Werner syndrome.

Journal of clinical lipidology
2022

WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer.

BioEssays : news and reviews in molecular, cellular and developmental biology
2022

Lifetime extension and the recent cause of death in Werner syndrome: a retrospective study from 2011 to 2020.

Orphanet journal of rare diseases
2022

XPG in the Nucleotide Excision Repair and Beyond: a study on the different functional aspects of XPG and its associated diseases.

Molecular biology reports
2022

Non-enzymatic function of WRN RECQL helicase regulates removal of topoisomerase-I-DNA covalent complexes and triggers NF-κB signaling in cancer.

Aging cell
2022

Targeted long-read sequencing identifies missing pathogenic variants in unsolved Werner syndrome cases.

Journal of medical genetics
2022

A Werner Syndrome with Psychiatric Symptoms: Case Report.

Psychiatria Danubina
2022

Radiotherapy and radiosensitivity syndromes in DNA repair gene mutations.

Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti
2022

SHP2's gain-of-function in Werner syndrome causes childhood disease onset likely resulting from negative genetic interaction.

Clinical genetics
2022

Combination immunotherapy of nivolumab plus ipilimumab in a lung cancer patient with Werner syndrome; a case report.

Respiratory medicine case reports
2022

Treatment of osteoporosis associated with Werner syndrome: A three-case report.

Geriatrics &amp; gerontology international
2023

A Patient with Werner's Syndrome Who Underwent Aortic Valve Replacement through Minimally Invasive Cardiac Surgery.

Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia
2022

A high prevalence of myeloid malignancies in progeria with Werner syndrome is associated with p53 insufficiency.

Experimental hematology
2022

R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1.

International journal of molecular sciences
2022

Paradoxical role of the major DNA repair protein, OGG1, in action-at-a-distance mutation induction by 8-oxo-7,8-dihydroguanine.

DNA repair
2022

DNA methylation signatures in Blood DNA of Hutchinson-Gilford Progeria syndrome.

Aging cell
2022

Werner syndrome in a Lebanese family.

American journal of medical genetics. Part A
2022

Cancer-Predisposition Genetic Analysis in Children with Brain Tumors Treated at a Single Institution in Japan.

Oncology
2021

Calcification in Werner syndrome associated with lymphatic vessels aging.

Aging
2021

Characterization of Stress Responses in a Drosophila Model of Werner Syndrome.

Biomolecules
2021

MUT-7 Provides Molecular Insight into the Werner Syndrome Exonuclease.

Cells
2022

Examination of the body composition of patients with Werner syndrome using bioelectrical impedance analysis.

Geriatrics &amp; gerontology international
2021

WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells.

Nature communications
2021

CDK2 phosphorylation of Werner protein (WRN) contributes to WRN's DNA double-strand break repair pathway choice.

Aging cell
2022

Werner syndrome presenting as early-onset diabetes: A case report.

Journal of diabetes investigation
2021

Generalized lipoatrophy syndromes.

Presse medicale (Paris, France : 1983)
2022

Atherosclerosis and Cardiovascular Diseases in Progeroid Syndromes.

Journal of atherosclerosis and thrombosis
2021

[Basic science of Werner syndrome].

Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics
2021

[Clinical advances in Werner syndrome].

Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics
2021

Human RecQL4 as a Novel Molecular Target for Cancer Therapy.

Cytogenetic and genome research
2021

Crosstalk among DNA Damage, Mitochondrial Dysfunction, Impaired Mitophagy, Stem Cell Attrition, and Senescence in the Accelerated Ageing Disorder Werner Syndrome.

Cytogenetic and genome research
2022

Reactive Species in Progeroid Syndromes and Aging-Related Processes.

Antioxidants &amp; redox signaling
2021

Type I Interferon Induction in Cutaneous DNA Damage Syndromes.

Frontiers in immunology
2021

The WRN helicase: resolving a new target in microsatellite unstable cancers.

Current opinion in genetics &amp; development
2021

Action-at-a-distance mutations at 5'-GpA-3' sites induced by oxidised guanine in WRN-knockdown cells.

Mutagenesis
2021

DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer's Disease.

International journal of molecular sciences
2021

Cerebral pathological findings in long-lived patient with Werner syndrome and dementia.

Geriatrics &amp; gerontology international
2021

Mutations Involved in Premature-Ageing Syndromes.

The application of clinical genetics
2021

Generation of disease-specific and CRISPR/Cas9-mediated gene-corrected iPS cells from a patient with adult progeria Werner syndrome.

Stem cell research
2021

Successful allogeneic stem cell transplantation of a patient with Werner syndrome and acute myeloid leukemia.

Leukemia research
2022

General anesthesia for old Werner syndrome patient: a case report.

Brazilian journal of anesthesiology (Elsevier)
Ver todos os 680 no EuropePMC

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Doenças relacionadas

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Referências e fontes

Bases de dados externas citadas neste artigo

Publicações científicas

Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.

  1. Deficiency of Werner RecQ-type DNA helicase causes premature malnutrition in zebrafish.
    iScience· 2026· PMID 41732282mais citado
  2. Unraveling syndrome-driven osteosarcoma: genetic insights and therapeutic frontiers.
    Orphanet journal of rare diseases· 2026· PMID 41652616mais citado
  3. Novel Homozygous Variants in CIDEC and WRN in a Young Female with Lipodystrophy and Thyroid Cancer.
    International journal of molecular sciences· 2026· PMID 41596298mais citado
  4. WRN structural flexibility showcased through fragment-based lead discovery of inhibitors.
    Nature communications· 2026· PMID 41484101mais citado
  5. Prognostic Significance of DNA Repair Gene mRNA Expression in Early-Stage Breast Cancer: Insights into Clinical Relevance.
    Oncology research· 2026· PMID 41799499mais citado
  6. Ocular Manifestations in Patients with Werner Syndrome.
    Int J Mol Sci· 2026· PMID 41977369recente
  7. Targeting WRN helicase in MSI-H tumors: Synthetic lethality, small molecule discovery, and therapeutic perspectives.
    Eur J Med Chem· 2026· PMID 41962327recente
  8. Discovery of WRN helicase inhibitors by 3D-CNN docking and ML consensus from traditional Chinese medicine monomers.
    J Mol Graph Model· 2026· PMID 41934827recente
  9. Preferential correction of target genes by 5'-tailed duplexes with an antisense editor strand.
    J Biosci Bioeng· 2026· PMID 41881702recente
  10. Werner Syndrome.
    · 1993· PMID 20301687recente

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:902(Orphanet)
  2. OMIM OMIM:277700(OMIM)
  3. MONDO:0010196(MONDO)
  4. GARD:7885(GARD (NIH))
  5. Variantes catalogadas(ClinVar)
  6. Busca completa no PubMed(PubMed)
  7. Artigo Wikipedia(Wikipedia)
  8. Q1154619(Wikidata)

Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.

Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar

Síndrome Werner
Compêndio · Raras BR

Síndrome Werner

ORPHA:902 · MONDO:0010196
Prevalência
1-9 / 1 000 000
Herança
Autosomal recessive
CID-10
E34.8 · Outros transtornos endócrinos especificados
CID-11
Ensaios
1 ativos
Início
Adolescent, Adult
Prevalência
0.5 (Europe)
MedGen
UMLS
C0043119
EuropePMC
Wikidata
Wikipedia
Papers 10a
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