1,373 results match your criteria Cockayne Syndrome

Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel variants.

Aging (Albany NY) 2022 Jun 22;14(undefined). Epub 2022 Jun 22.

Friedrich-Baur-Institute, Department of Neurology, LMU Klinikum, Ludwig-Maximilians-University Munich, Munich, Germany.

Cockayne syndrome (CS) is a rare progeroid disorder characterized by growth failure, microcephaly, photosensitivity, and premature aging, mainly arising from biallelic (CS-A) or (CS-B) variants. In this study we describe siblings suffering from classical Cockayne syndrome but without photosensitivity, which delayed a clinical diagnosis for 16 years. By whole-exome sequencing we identified the two novel compound heterozygous variants c. Read More

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Cockayne syndrome group B protein uses its DNA translocase activity to promote mitotic DNA synthesis.

DNA Repair (Amst) 2022 Jun 17;116:103354. Epub 2022 Jun 17.

Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada. Electronic address:

Mitotic DNA synthesis, also known as MiDAS, has been suggested to be a form of RAD52-dependent break-induced replication (BIR) that repairs under-replicated DNA regions of the genome in mitosis prior to chromosome segregation. Cockayne syndrome group B (CSB) protein, a chromatin remodeler of the SNF2 family, has been implicated in RAD52-dependent BIR repair of stalled replication forks. However, whether CSB plays a role in MiDAS has not been characterized. Read More

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Adult-Onset Neurodegeneration in Nucleotide Excision Repair Disorders (NERD ): Time to Move Beyond the Skin.

Mov Disord 2022 Jun 14. Epub 2022 Jun 14.

Department of Neurology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.

Background: Variants in genes of the nucleotide excision repair (NER) pathway have been associated with heterogeneous clinical presentations ranging from xeroderma pigmentosum to Cockayne syndrome and trichothiodystrophy. NER deficiencies manifest with photosensitivity and skin cancer, but also developmental delay and early-onset neurological degeneration. Adult-onset neurological features have been reported in only a few xeroderma pigmentosum cases, all showing at least mild skin manifestations. Read More

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Whole-exome sequencing revealed a novel ERCC6 variant in a Vietnamese patient with Cockayne syndrome.

Hum Genome Var 2022 Jun 6;9(1):21. Epub 2022 Jun 6.

Yokohama City University Graduate School of Medicine, Yokohama, Japan.

We describe a case of Cockayne syndrome without photosensitivity in a Vietnamese family. This lack of photosensitivity prevented the establishment of a confirmed medical clinical diagnosis for 16 years. Whole-exome sequencing (WES) identified a novel missense variant combined with a known nonsense variant in the ERCC6 gene, NM_000124. Read More

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Whole exome sequencing identifies a novel variant causing cockayne syndrome type I in a consanguineous Pakistani family.

Int J Neurosci 2022 Jun 12:1-6. Epub 2022 Jun 12.

National Institute for Biotechnology and Genetic Engineering College (NIBGE-C), Faisalabad, Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad, Pakistan.

Background: Cockayne syndrome (CS) is a rare neurodegenerative disorder characterized by impaired neurological functions, cachectic dwarfism, microcephaly and photosensitivity. Complementation assays identify two groups of this disorder, CS type I (CSA) and CS type II (CSB), caused by mutations in ERCC8 and ERCC6, respectively.

Objectives: This study aimed to investigate the genetic basis of a consanguineous Pakistani family with three affected individuals presenting with typical clinical symptoms of CS. Read More

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Metronidazole-induced hepatotoxicity in a patient with xeroderma pigmentosum: A case report.

Medicine (Baltimore) 2022 May 27;101(21):e29416. Epub 2022 May 27.

University Milano-Bicocca, Milan, Italy.

Rationale: Whereas metronidazole-induced hepatotoxicity is quite rare in the general population, in individuals carrying a nucleotide excision repair disorder, namely Cockayne syndrome, there is a high risk of developing this complication.

Patient Concerns: We report the case of a 44-year-old man, affected by xeroderma pigmentosum, who was admitted to the hospital presenting aspiration pneumoniae caused by worsening dysphagia and with severe hepatotoxicity during the hospitalization.

Diagnoses: Acute hepatitis, which was leading to acute liver failure, occurred during antibiotic treatment with metronidazole and ceftazidime with an elevation of liver enzymes consistent with hepatocellular damage pattern. Read More

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Keeping COFs in the loop.

Nat Chem 2022 May;14(5):485-486

Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA.

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Radiotherapy and radiosensitivity syndromes in DNA repair gene mutations.

Klin Onkol 2022 ;35(2):119-127

Background: Ionizing radiation DNA damage is the main mechanism of radiotherapy (RT) action and the outcome of treatment and healthy tissue toxicity is influenced by a number of external and internal factors, including mutations in DNA damage recognition and repair. Disorders of DNA repair may result in increased sensitivity to cancer treatment.

Purpose: The mechanism of DNA repair and an overview of genetic syndromes with mutations in genes involved in DNA repair clarify the accelerated carcinogenesis and increased radiosensitivity in RT cancers. Read More

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Effects of Oxygen Tension for Membrane Lipidome Remodeling of Cockayne Syndrome Cell Models.

Cells 2022 04 10;11(8). Epub 2022 Apr 10.

Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy.

Oxygen is important for lipid metabolism, being involved in both enzymatic transformations and oxidative reactivity, and is particularly influent when genetic diseases impair the repair machinery of the cells, such as described for Cockayne syndrome (CS). We used two cellular models of transformed fibroblasts defective for CSA and CSB genes and their normal counterparts, grown for 24 h under various oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%) to examine the fatty acid-based membrane remodeling by GC analysis of fatty acid methyl esters derived from membrane phospholipids. Overall, we first distinguished differences due to oxygen tensions: (a) hyperoxia induced a general boost of desaturase enzymatic activity in both normal and defective CSA and CSB cell lines, increasing monounsaturated fatty acids (MUFA), whereas polyunsaturated fatty acids (PUFA) did not undergo oxidative consumption; (b) hypoxia slowed down desaturase activities, mostly in CSA cell lines and defective CSB, causing saturated fatty acids (SFA) to increase, whereas PUFA levels diminished, suggesting their involvement in hypoxia-related signaling. Read More

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CSA Antisense Targeting Enhances Anticancer Drug Sensitivity in Breast Cancer Cells, including the Triple-Negative Subtype.

Cancers (Basel) 2022 Mar 26;14(7). Epub 2022 Mar 26.

Laboratory of Molecular Genetics of Aging, Department of Ecology and Biology, University of Tuscia, 01100 Viterbo, Italy.

Breast cancer (BC) is the most common cancer with the highest frequency of death among women. BC is highly heterogenic at the genetic, biological, and clinical level. Despite the significant improvements in diagnosis and treatments of BC, the high rate of cancer recurrence and resistance to treatment remains a major challenge in clinical practice. Read More

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Camptothecin compromises transcription recovery and cell survival against cisplatin and ultraviolet irradiation regardless of transcription-coupled nucleotide excision repair.

DNA Repair (Amst) 2022 Mar 10;113:103318. Epub 2022 Mar 10.

Department of Biochemistry I, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan. Electronic address:

DNA-damaging anti-cancer drugs are used clinically to induce cell death by causing DNA strand breaks or DNA replication stress. Camptothecin (CPT) and cisplatin are commonly used anti-cancer drugs, and their combined use enhances the anti-tumour effects. However, the mechanism underlying this enhanced effect has not been well studied. Read More

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The UVSSA protein is part of a genome integrity homeostasis network with links to transcription-coupled DNA repair and ATM signaling.

Proc Natl Acad Sci U S A 2022 03 7;119(11):e2116254119. Epub 2022 Mar 7.

Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA 01605.

SignificanceTranscription-coupled repair (TCR) involves four core proteins: CSA, CSB, USP7, and UVSSA. CSA and CSB are mutated in the severe human neurocutaneous disease Cockayne syndrome. In contrast UVSSA is a mild photosensitive disease in which a mutated protein sequence prevents recruitment of USP7 protease to deubiquitinate and stabilize CSB. Read More

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Statistical Approach of the Role of the Conserved CSB-PiggyBac Transposase Fusion Protein (CSB-PGBD3) in Genotype-Phenotype Correlation in Cockayne Syndrome Type B.

Front Genet 2022 17;13:762047. Epub 2022 Feb 17.

Laboratoire de Génétique Médicale, Institut de Génétique Médicale d'Alsace, Faculté de Médecine de Strasbourg, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Cockayne syndrome is a rare condition that encompasses a very wide spectrum of clinical severity. Mutations upstream of a transposon called PiggyBac Transposable Element Derived 3 in intron 5 of the gene could bring about less severe forms than mutations located downstream of that transposon insertion. Our aim was to study genotype-phenotype correlation by determining whether the position of each mutation of the gene has an impact on the phenotype. Read More

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February 2022

Heterogeneous clinical features in Cockayne syndrome patients and siblings carrying the same CSA mutations.

Orphanet J Rare Dis 2022 03 5;17(1):121. Epub 2022 Mar 5.

Laboratory of Biomedical Genomics and Oncogenetics (LR20IPT05), Institut Pasteur de Tunis, Université Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur, 1002, Tunis-Belvedere, Tunisia.

Background: Cockayne syndrome (CS) is a rare autosomal recessive disorder caused by mutations in ERCC6/CSB or ERCC8/CSA that participate in the transcription-coupled nucleotide excision repair (TC-NER) of UV-induced DNA damage. CS patients display a large heterogeneity of clinical symptoms and severities, the reason of which is not fully understood, and that cannot be anticipated in the diagnostic phase. In addition, little data is available for affected siblings, and this disease is largely undiagnosed in North Africa. Read More

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XPG: a multitasking genome caretaker.

Cell Mol Life Sci 2022 Mar 1;79(3):166. Epub 2022 Mar 1.

Department of Molecular Genetics, Erasmus MC Cancer Institute, Oncode Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.

The XPG/ERCC5 endonuclease was originally identified as the causative gene for Xeroderma Pigmentosum complementation group G. Ever since its discovery, in depth biochemical, structural and cell biological studies have provided detailed mechanistic insight into its function in excising DNA damage in nucleotide excision repair, together with the ERCC1-XPF endonuclease. In recent years, it has become evident that XPG has additional important roles in genome maintenance that are independent of its function in NER, as XPG has been implicated in protecting replication forks by promoting homologous recombination as well as in resolving R-loops. Read More

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Dynamic Interplay between Cockayne Syndrome Protein B and Poly(ADP-Ribose) Polymerase 1 during Oxidative DNA Damage Repair.

Biomedicines 2022 Feb 2;10(2). Epub 2022 Feb 2.

Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA.

Oxidative stress contributes to numerous diseases, including cancer. CSB is an ATP-dependent chromatin remodeler critical for oxidative stress relief. PARP1 is the major sensor for DNA breaks and fundamental for efficient single-strand break repair. Read More

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February 2022

Integrated genome and transcriptome analyses reveal the mechanism of genome instability in ataxia with oculomotor apraxia 2.

Proc Natl Acad Sci U S A 2022 01;119(4)

DNA Recombination and Repair Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom;

Mutations in the gene, which encodes Senataxin, are associated with the progressive neurodegenerative diseases ataxia with oculomotor apraxia 2 (AOA2) and amyotrophic lateral sclerosis 4 (ALS4). To identify the causal defect in AOA2, patient-derived cells and knockouts (human and mouse) were analyzed using integrated genomic and transcriptomic approaches. A genome-wide increase in chromosome instability (gains and losses) within genes and at chromosome fragile sites was observed, resulting in changes to gene-expression profiles. Read More

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January 2022

Identification and Characterization of a Novel Recurrent Variant in Patients with a Severe Form of Cockayne Syndrome B.

Genes (Basel) 2021 11 29;12(12). Epub 2021 Nov 29.

Laboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, Université Tunis El Manar, El Manar I, Tunis 1002, Tunisia.

Cockayne syndrome (CS) is a rare disease caused by mutations in / or /. We report here the clinical, genetic, and functional analyses of three unrelated patients mutated in / with a severe phenotype. After clinical examination, two patients were investigated via next generation sequencing, targeting seventeen Nucleotide Excision Repair (NER) genes. Read More

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November 2021

Embryonal sarcoma of the liver in a girl with Cockayne syndrome.

Clin Genet 2022 03 8;101(3):375-376. Epub 2021 Dec 8.

Department of Paediatric Haematology and Oncology, Royal Manchester Children's Hospital, Manchester NHS Foundation Trust Manchester, Manchester, UK.

The first reported malignancy associated with Cockayne syndrome. Read More

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Cockayne syndrome group B protein regulates fork restart, fork progression and MRE11-dependent fork degradation in BRCA1/2-deficient cells.

Nucleic Acids Res 2021 12;49(22):12836-12854

Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.

Cockayne syndrome group B (CSB) protein has been implicated in the repair of a variety of DNA lesions that induce replication stress. However, little is known about its role at stalled replication forks. Here, we report that CSB is recruited to stalled forks in a manner dependent upon its T1031 phosphorylation by CDK. Read More

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December 2021

Cockayne Syndrome B Protein Selectively Resolves and Interact with Intermolecular DNA G-Quadruplex Structures.

J Am Chem Soc 2021 12 2;143(49):20988-21002. Epub 2021 Dec 2.

Chemistry Department, Imperial College London, Molecular Science Research Hub, 82 Wood Lane, London W12 0BZ, United Kingdom.

Guanine-rich DNA can fold into secondary structures known as G-quadruplexes (G4s). G4s can form from a single DNA strand (intramolecular) or from multiple DNA strands (intermolecular), but studies on their biological functions have been often limited to intramolecular G4s, owing to the low probability of intermolecular G4s to form within genomic DNA. Herein, we report the first example of an endogenous protein, Cockayne Syndrome B (CSB), that can bind selectively with picomolar affinity toward intermolecular G4s formed within rDNA while displaying negligible binding toward intramolecular structures. Read More

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December 2021

Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair.

Nat Commun 2021 12 1;12(1):7001. Epub 2021 Dec 1.

Department of Chemistry, Georgia State University, Atlanta, GA, USA.

Transcription-coupled repair is essential for the removal of DNA lesions from the transcribed genome. The pathway is initiated by CSB protein binding to stalled RNA polymerase II. Mutations impairing CSB function cause severe genetic disease. Read More

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December 2021

Whole Exome Sequencing Identifies a Novel Homozygous Missense Mutation in the CSB Protein-Encoding Gene in a Taiwanese Boy with Cockayne Syndrome.

Life (Basel) 2021 Nov 14;11(11). Epub 2021 Nov 14.

Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.

Background: Cockayne syndrome (CS) is a rare form of dwarfism that is characterized by progressive premature aging. CS is typically caused by mutations in the excision repair cross-complementing protein group 6 () gene that encodes the CS group B (CSB) protein. Using whole exome sequencing, we recently identified a novel homozygous missense mutation (Leu536Trp) in CSB in a Taiwanese boy with CS. Read More

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November 2021

Aldehyde-driven transcriptional stress triggers an anorexic DNA damage response.

Nature 2021 12 24;600(7887):158-163. Epub 2021 Nov 24.

MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Endogenous DNA damage can perturb transcription, triggering a multifaceted cellular response that repairs the damage, degrades RNA polymerase II and shuts down global transcription. This response is absent in the human disease Cockayne syndrome, which is caused by loss of the Cockayne syndrome A (CSA) or CSB proteins. However, the source of endogenous DNA damage and how this leads to the prominent degenerative features of this disease remain unknown. Read More

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December 2021

Hepatotoxicity of metronidazole in Cockayne syndrome: A clinical report.

Eur J Med Genet 2022 Jan 9;65(1):104388. Epub 2021 Nov 9.

Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Reims, 51100, Reims, France. Electronic address:

Cockayne syndrome (CS) is a rare autosomal recessive genetic disorder characterized by growth failure and progressive multisystem dysfunction caused by deficient nucleotide excision repair. Whereas metronidazole (MTZ) hepatotoxicity is quite rare in the general population, cases of severe hepatic reaction to MTZ have been reported in CS patients. We report here the case of a 21-year-old CS patient who presented with jaundice following one week of treatment with MTZ combined with spiramycin for dental care. Read More

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January 2022

Functions of the CSB Protein at Topoisomerase 2 Inhibitors-Induced DNA Lesions.

Front Cell Dev Biol 2021 22;9:727836. Epub 2021 Oct 22.

Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil.

Topoisomerase 2 (TOP2) inhibitors are drugs widely used in the treatment of different types of cancer. Processing of their induced-lesions create double-strand breaks (DSBs) in the DNA, which is the main toxic mechanism of topoisomerase inhibitors to kill cancer cells. It was established that the Nucleotide Excision Repair pathway respond to TOP2-induced lesions, mainly through the Cockayne Syndrome B (CSB) protein. Read More

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October 2021

Cockayne syndrome type: a very rare association with hemorrhagic stroke.

Turk J Pediatr 2021;63(5):922-926

Departments of Pediatric Neurology, İstanbul Medeniyet University Faculty of Medicine, Göztepe Training and Research Hospital, İstanbul, Turkey.

Background: Cockayne Syndrome (CS) is a rare autosomal recessive disorder that is mainly characterized by neurodevelopmental delay, cutaneous photosensitivity, and cachectic dwarfism. Genetic diagnosis is supported by the typical physical appearance and imaging findings of these patients.

Case: In our case, a 16-year-old female previously diagnosed as CS presented with right-sided hemiparesis. Read More

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January 2022