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    1199 results match your criteria Cockayne Syndrome

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    Temporal Bone Histopathology in Cockayne Syndrome.
    Otol Neurotol 2018 Apr 11. Epub 2018 Apr 11.
    Otopathology Laboratory, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
    : Cockayne syndrome (CS) is a rare autosomal recessive syndrome resulting in defective DNA repair. Its features include cachectic dwarfism, hearing loss, skin hypersensitivity to sunlight, premature aging, and dementia. Presented is a right temporal bone of a patient who died at the age of 29 years. Read More

    Generation of splice switching oligonucleotides targeting the Cockayne syndrome group B gene product in order to change the diseased cell state.
    Biochem Biophys Res Commun 2018 Apr 9. Epub 2018 Apr 9.
    National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
    Cockayne syndrome (CS) is a severe disorder with no effective treatment. The Cockayne syndrome group B (CSB) gene is one gene responsible for CS and also causes UV sensitive syndrome (UVS), a disorder that causes mild symptoms. How the CSB gene determines a patient's fate is unknown, but one intriguing point is that in UVS patient cell, there are nonsense mutations in both alleles at the same position in each upstream region of the PiggyBac transposable element derived 3 (PGBD3) inserted region. Read More

    Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome.
    J Med Genet 2018 Mar 23. Epub 2018 Mar 23.
    Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
    Background: Cockayne syndrome (CS) is a rare, autosomal recessive multisystem disorder characterised by prenatal or postnatal growth failure, progressive neurological dysfunction, ocular and skeletal abnormalities and premature ageing. About half of the patients with symptoms diagnostic for CS show cutaneous photosensitivity and an abnormal cellular response to UV light due to mutations in either the / or / gene. Studies performed thus far have failed to delineate clear genotype-phenotype relationships. Read More

    CSA and CSB play a role in the response to DNA breaks.
    Oncotarget 2018 Feb 29;9(14):11581-11591. Epub 2018 Jan 29.
    Section of Mechanisms, Biomarkers and Models, Department of Environment and Health, Istituto Superiore di Sanità, Roma, Italy.
    CS proteins have been involved in the repair of a wide variety of DNA lesions. Here, we analyse the role of CS proteins in DNA break repair by studying histone H2AX phosphorylation in different cell cycle phases and DNA break repair by comet assay in CS-A and CS-B primary and transformed cells. Following methyl methane sulphate treatment a significant accumulation of unrepaired single strand breaks was detected in CS cells as compared to normal cells, leading to accumulation of double strand breaks in S and G2 phases. Read More

    TRiC controls transcription resumption after UV damage by regulating Cockayne syndrome protein A.
    Nat Commun 2018 03 12;9(1):1040. Epub 2018 Mar 12.
    Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, Leiden, 2333 ZC, The Netherlands.
    Transcription-blocking DNA lesions are removed by transcription-coupled nucleotide excision repair (TC-NER) to preserve cell viability. TC-NER is triggered by the stalling of RNA polymerase II at DNA lesions, leading to the recruitment of TC-NER-specific factors such as the CSA-DDB1-CUL4A-RBX1 cullin-RING ubiquitin ligase complex (CRL). Despite its vital role in TC-NER, little is known about the regulation of the CRL complex during TC-NER. Read More

    CSB: An Emerging Actionable Target for Cancer Therapy.
    Trends Cancer 2018 Mar 23;4(3):172-175. Epub 2018 Feb 23.
    Unit of Molecular Genetics of Aging and Laboratory of Epigenetics, Department of Ecology and Biology, University of Tuscia, 01100 Viterbo, Italy.
    The DNA repair protein Cockayne syndrome group B (CSB) is frequently found overexpressed in cancer cells. High CSB levels favor tumor cell proliferation whilst inhibiting apoptosis. Conversely, the suppression of CSB has significant anticancer effects. Read More

    Cochlear implantation in pediatric patients with Cockayne Syndrome.
    Int J Pediatr Otorhinolaryngol 2018 Mar 30;106:64-67. Epub 2017 Dec 30.
    Dell Medical School at the University of Texas at Austin, Department of Otolaryngology/ENT, 6811 Austin Center Blvd Suite 300, Austin, TX 78731, USA. Electronic address:
    Cockayne Syndrome (CS) is a rare, autosomal recessive disorder characterized by a spectrum of phenotypic abnormalities, including progressive sensorineural hearing loss (SNHL) that involves both peripheral and central components. To date, a single series of CS patients undergoing cochlear implant (CI) placement has been reported; this study reports on additional previously unreported pediatric CI recipients. Subjective benefits were noted early after activation in both patients, and speech perception scores improved over time as well, varying from 42 to 70% (versus 0-12% previously). Read More

    Deep intronic variation in splicing regulatory element of the ERCC8 gene associated with severe but long-term survival Cockayne syndrome.
    Eur J Hum Genet 2018 Apr 8;26(4):527-536. Epub 2018 Feb 8.
    Laboratoire de Diagnostic Génétique, Institut de Génétique Médicale d'Alsace (IGMA), Hôpitaux Universitaires de Strasbourg, 1 place de l'hôpital, Strasbourg, 67091, France.
    Cockayne syndrome is an autosomal recessive multisystem disorder characterized by intellectual disability, microcephaly, severe growth failure, sensory impairment, peripheral neuropathy, and cutaneous sensitivity. This rare disease is linked to disease-causing variations in the ERCC6 (CSB) and ERCC8 (CSA) genes. Various degrees of severity have been described according to age at onset and survival, without any clear genotype-phenotype correlation. Read More

    Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations.
    J Hum Genet 2018 Apr 5;63(4):417-423. Epub 2018 Feb 5.
    Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
    Autosomal recessive cerebellar ataxias (ARCAs) are clinically and genetically heterogeneous neurological disorders. Through whole-exome sequencing of Japanese ARCA patients, we identified three index patients from unrelated families who had biallelic mutations in ERCC4. ERCC4 mutations have been known to cause xeroderma pigmentosum complementation group F (XP-F), Cockayne syndrome, and Fanconi anemia phenotypes. Read More

    Are parents of children with Cockayne syndrome manifesting features of the disorder?: Case reports.
    Medicine (Baltimore) 2017 Dec;96(50):e8970
    Institute of Medical Chemistry, Medical University of Vienna, Vienna, Austria.
    Rationale: Postnatal growth failure and progressive neurologic dysfunction and increasing multiorgan involvement are the main clinical features of Cockayne syndrome (CS). CS is a rare autosomal recessive disorder of the group of DNA repair diseases. Usually, genetic carriers, such as parents of patients, are not at risk for developing the disease. Read More

    Fanconi anemia with sun-sensitivity caused by a Xeroderma pigmentosum-associated missense mutation in XPF.
    BMC Med Genet 2018 Jan 11;19(1). Epub 2018 Jan 11.
    Department of Human Genetics, Biozentrum, University of Wurzburg, Am Hubland, 97074, Wurzburg, Germany.
    Background: Fanconi anemia (FA) is an inherited genomic instability disorder with congenital and developmental abnormalities, bone marrow failure and predisposition to cancer early in life, and cellular sensitivity to DNA interstrand crosslinks.

    Case Presentation: A fifty-one-year old female patient, initially diagnosed with FA in childhood on the basis of classic features and increased chromosomal breakage, and remarkable sun-sensitivity is described. She only ever had mild haematological abnormalities and no history of malignancy. Read More

    Actual state of knowledge in the field of diseases related with defective nucleotide excision repair.
    Life Sci 2018 Feb 2;195:6-18. Epub 2018 Jan 2.
    Food Science Department, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
    Xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS) are rare genetic diseases characterized by a large range of clinical symptoms. However, they are all associated with defects in nucleotide excision repair (NER), the system responsible for removing bulky DNA lesions such as those generated by UV light: cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone photoproducts (6-4 PPs). Over the past years, detailed structural and biochemical information on NER-associated proteins has emerged. Read More

    RNA polymerase II is released from the DNA template during transcription-coupled repair in mammalian cells.
    J Biol Chem 2018 Feb 27;293(7):2476-2486. Epub 2017 Dec 27.
    From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260 and.
    In mammalian cells, bulky DNA adducts located in the template but not the coding strand of genes block elongation by RNA polymerase II (RNAPII). The blocked RNAPII targets these transcription-blocking adducts to undergo more rapid excision repair than adducts located elsewhere in the genome. In excision repair, coupled incisions are made in the damaged DNA strand on both sides of the adduct. Read More

    Role of mitochondrial dysfunction in the pathophysiology of DNA repair disorders.
    Cell Biol Int 2017 Dec 22. Epub 2017 Dec 22.
    Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo (USP), São Paulo, SP, Brazil.
    DNA is constantly being damaged, either by endogenous or exogenous genotoxins. In that regard, DNA repair activities are essential for maintaining genomic stability and to life itself. Mutations in genes encoding DNA repair proteins cause severe human syndromes, but DNA repair defects have also been linked to several other diseases, notably to cancer and normal aging. Read More

    Cockayne's Syndrome A and B Proteins Regulate Transcription Arrest after Genotoxic Stress by Promoting ATF3 Degradation.
    Mol Cell 2017 Dec 7;68(6):1054-1066.e6. Epub 2017 Dec 7.
    IGBMC, Department of Functional Genomics and Cancer, Equipe Labellisée Ligue 2014, CNRS/INSERM/University of Strasbourg, BP 163, 67404 Illkirch Cedex, C.U. Strasbourg, France; Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France; Université de Strasbourg, 67404 Illkirch, France. Electronic address:
    Cockayne syndrome (CS) is caused by mutations in CSA and CSB. The CSA and CSB proteins have been linked to both promoting transcription-coupled repair and restoring transcription following DNA damage. We show that UV stress arrests transcription of approximately 70% of genes in CSA- or CSB-deficient cells due to the constitutive presence of ATF3 at CRE/ATF sites. Read More

    Aging and neurodegeneration are associated with increased mutations in single human neurons.
    Science 2018 02 7;359(6375):555-559. Epub 2017 Dec 7.
    Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
    It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. Read More

    SIRT2 and Akt mediate NAD+-induced and NADH-induced increases in the intracellular ATP levels of BV2 microglia under basal conditions.
    Neuroreport 2018 Jan;29(2):65-70
    School of Biomedical Engineering, Med-X Research Institute, Division of Disease Studies, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    NAD replenishment can restore ATP levels and rescue premature aging in Cockayne syndrome mice. However, there has been no mechanistic study regarding the effects of NAD and NADH on intracellular ATP levels under basal conditions. In our current study, we used BV2 microglia to test our hypothesis that NAD and NADH can increase intracellular ATP levels under basal conditions. Read More

    Structural basis for the initiation of eukaryotic transcription-coupled DNA repair.
    Nature 2017 11 22;551(7682):653-657. Epub 2017 Nov 22.
    Division of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, USA.
    Eukaryotic transcription-coupled repair (TCR) is an important and well-conserved sub-pathway of nucleotide excision repair that preferentially removes DNA lesions from the template strand that block translocation of RNA polymerase II (Pol II). Cockayne syndrome group B (CSB, also known as ERCC6) protein in humans (or its yeast orthologues, Rad26 in Saccharomyces cerevisiae and Rhp26 in Schizosaccharomyces pombe) is among the first proteins to be recruited to the lesion-arrested Pol II during the initiation of eukaryotic TCR. Mutations in CSB are associated with the autosomal-recessive neurological disorder Cockayne syndrome, which is characterized by progeriod features, growth failure and photosensitivity. Read More

    Omics Approaches for Identifying Physiological Adaptations to Genome Instability in Aging.
    Int J Mol Sci 2017 Nov 4;18(11). Epub 2017 Nov 4.
    Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
    DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. Read More

    ERCC4 variants identified in a cohort of patients with segmental progeroid syndromes.
    Hum Mutat 2018 Feb 17;39(2):255-265. Epub 2017 Nov 17.
    Department of Pathology, University of Washington, Seattle, Washington.
    Pathogenic variants in genes, which encode DNA repair and damage response proteins, result in a number of genomic instability syndromes with features of accelerated aging. ERCC4 (XPF) encodes a protein that forms a complex with ERCC1 and is required for the 5' incision during nucleotide excision repair. ERCC4 is also FANCQ, illustrating a critical role in interstrand crosslink repair. Read More

    Molecular spectrum of excision repair cross-complementation group 8 gene defects in Chinese patients with Cockayne syndrome type A.
    Sci Rep 2017 Oct 20;7(1):13686. Epub 2017 Oct 20.
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China.
    There are two genetics complementary groups Cockayne syndrome type A and B (CS-A and CS-B OMIM 216400, 133540), which is a rare autosomal recessive segmental progeroid syndrome. Homozygous or compound heterozygous mutations in the excision repair cross-complementation group 8 gene (ERCC8) result in CS-A, and mutations in ERCC6 result in CS-B. Homozygous ERCC6/ERCC8 mutations also result in UV-sensitive syndrome. Read More

    Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.
    Neurobiol Aging 2018 Jan 12;61:215-224. Epub 2017 Aug 12.
    Center for Neuroscience, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Neurophysiology, Rigshospitalet, Glostrup, Denmark; Center of Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB hippocampus, but not in CSB cortex or WT brain. Read More

    The cryo-electron microscopy structure of human transcription factor IIH.
    Nature 2017 09 13;549(7672):414-417. Epub 2017 Sep 13.
    California Institute for Quantitative Biology (QB3), University of California, Berkeley, California 94720, USA.
    Human transcription factor IIH (TFIIH) is part of the general transcriptional machinery required by RNA polymerase II for the initiation of eukaryotic gene transcription. Composed of ten subunits that add up to a molecular mass of about 500 kDa, TFIIH is also essential for nucleotide excision repair. The seven-subunit TFIIH core complex formed by XPB, XPD, p62, p52, p44, p34, and p8 is competent for DNA repair, while the CDK-activating kinase subcomplex, which includes the kinase activity of CDK7 as well as the cyclin H and MAT1 subunits, is additionally required for transcription initiation. Read More

    A Novel Mutation in Gene Causing Cockayne Syndrome.
    Front Pediatr 2017 9;5:169. Epub 2017 Aug 9.
    Center for Therapeutic Innovation, Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, United States.
    Cockayne syndrome (CS) is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Read More

    Transcription coupled repair deficiency protects against human mutagenesis and carcinogenesis: Personal Reflections on the 50th anniversary of the discovery of xeroderma pigmentosum.
    DNA Repair (Amst) 2017 10 23;58:21-28. Epub 2017 Aug 23.
    Department of Dermatology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA, 94143. Electronic address:
    Xeroderma pigmentosum (XP) patients who lack the main damage recognition protein for global genome repair (GGR), XPC, have greatly increased skin cancer rates and elevated mutation frequencies originating from unrepaired ultraviolet photoproducts in the nontranscribed regions of the genome and in nontranscribed strands of expressed genes. But they show no increased mutations in transcribed strands. In contrast, cancer is absent from Cockayne syndrome (CS) patients that have defective transcription coupled repair (TCR) despite severe photosensitivity, CS patients remarkably show no elevation of UV induced mutagenesis implying that defective TCR may be protective against mutagenesis and carcinogenesis. Read More

    Increased oxidative phosphorylation in response to acute and chronic DNA damage.
    NPJ Aging Mech Dis 2016 13;2:16022. Epub 2016 Oct 13.
    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
    Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient mouse model of CS. Read More

    Cellular sensitivity to UV-irradiation is mediated by RNA polymerase I transcription.
    PLoS One 2017 21;12(6):e0179843. Epub 2017 Jun 21.
    Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
    The nucleolus has long been considered to be a pure ribosome factory. However, over the last two decades it became clear that the nucleolus is involved in numerous other functions besides ribosome biogenesis. Our experiments indicate that the activity of RNA polymerase I (Pol I) transcription monitors the integrity of the DNA and influences the response to nucleolar stress as well as the rate of survival. Read More

    Renal Involvement in 2 Siblings With Cockayne Syndrome.
    Iran J Kidney Dis 2017 May;11(3):253-255
    Department of Pediatrics, La Rabta Hospital; Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
    Renal involvement in Cockayne syndrome is rare and its pathogenesis is yet unknown. We report herein 2 cases (siblings) with Cockayne syndrome type A confirmed by biochemical and molecular assays. The first case was a 13-year-old girl who presented with nephritic syndrome and a rapidly progressive kidney failure. Read More

    Two novel mutations in ERCC6 cause Cockayne syndrome B in a Chinese family.
    Mol Med Rep 2017 Jun 20;15(6):3957-3962. Epub 2017 Apr 20.
    Department of Biochemistry and Molecular Biology, Center for DNA Typing, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
    Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized principally by progressive growth failure, neurologic abnormality and premature aging. Mutations of excision repair cross‑complementation group 6 (ERCC6) and ERCC8 are predominantly responsible for CS, of which mutation of ERCC6 accounts for approximately two thirds of cases. The current report describes two siblings with severe neurologic abnormality and premature aging. Read More

    Xeroderma pigmentosum-Cockayne syndrome complex.
    Orphanet J Rare Dis 2017 04 4;12(1):65. Epub 2017 Apr 4.
    Forgotten Diseases Research Foundation, Santa Clara, CA, 95050, USA.
    Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem degenerative disorder (Orpha: 220295; OMIM: 278730, 278760, 278780, 610651). Published information on XP-CS is mostly scattered throughout the literature. We compiled statistics related to symptom prevalence in XP-CS and have written a clinical description of the syndrome. Read More

    NAP1L1 accelerates activation and decreases pausing to enhance nucleosome remodeling by CSB.
    Nucleic Acids Res 2017 May;45(8):4696-4707
    Department of Physics and Astronomy, Seoul National University, Seoul 08826, Republic of Korea.
    Cockayne syndrome protein B (CSB) belongs to the SWI2/SNF2 ATP-dependent chromatin remodeler family, and CSB is the only ATP-dependent chromatin remodeler essential for transcription-coupled nucleotide excision DNA repair. CSB alone remodels nucleosomes ∼10-fold slower than the ACF remodeling complex. Strikingly, NAP1-like histone chaperones interact with CSB and greatly enhance CSB-mediated chromatin remodeling. Read More

    A complex intragenic rearrangement of ERCC8 in Chinese siblings with Cockayne syndrome.
    Sci Rep 2017 Mar 23;7:44271. Epub 2017 Mar 23.
    Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
    Cockayne syndrome is an autosomal recessive disorder principally characterized by postnatal growth failure and progressive neurological dysfunction, due primarily to mutations in ERCC6 and ERCC8. Here, we report our diagnostic experience for two patients in a Chinese family suspected on clinical grounds to have Cockayne syndrome. Using multiple molecular techniques, including whole exome sequencing, array comparative genomic hybridization and quantitative polymerase chain reaction, we identified compound heterozygosity for a maternal splicing variant (chr5:60195556, NM_000082:c. Read More

    Cockayne syndrome B protein regulates recruitment of the Elongin A ubiquitin ligase to sites of DNA damage.
    J Biol Chem 2017 04 14;292(16):6431-6437. Epub 2017 Mar 14.
    From the Stowers Institute for Medical Research, Kansas City, Missouri 64110,
    Elongin A performs dual functions as the transcriptionally active subunit of RNA polymerase II (Pol II) elongation factor Elongin and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase that ubiquitylates Pol II in response to DNA damage. Assembly of the Elongin A ubiquitin ligase and its recruitment to sites of DNA damage is a tightly regulated process induced by DNA-damaging agents and α-amanitin, a drug that induces Pol II stalling. In this study, we demonstrate (i) that Elongin A and the ubiquitin ligase subunit CUL5 associate in cells with the Cockayne syndrome B (CSB) protein and (ii) that this interaction is also induced by DNA-damaging agents and α-amanitin. Read More

    [The place of neuropathy in the early diagnosis of Cockayne syndrome: Report on two siblings].
    Arch Pediatr 2017 Apr 28;24(4):353-359. Epub 2017 Feb 28.
    Service de neurologie et réanimation pédiatriques, hôpital Raymond-Poincaré, hôpitaux universitaires Paris-Île-de-France Ouest, AP-HP, 104, boulevard Raymond-Poincaré, 92380 Garches, France; Centre de référence de maladies neuromusculaires Garches-Necker-Mondor-Hendaye (GNMH), France; U1179 UVSQ - Inserm, université de Versailles-Saint-Quentin, 78180 Montigny, France; FILNEMUS, Réseau national français de la filière neuromusculaire, France.
    Two siblings affected with Cockayne syndrome (CS) are described: this diagnosis was suggested by the finding of a demyelinating neuropathy on electromyography in both children and consistent clinical features. CS is a rare genetic disorder with severe prognosis and a highly varied phenotype, making early diagnosis difficult. Taking into account these two cases and the literature, the current diagnosis criteria are insufficiently specific and appear late: the diagnosis may be delayed because multi-organ involvement and sensorial impairment suggests more frequent neurometabolic disorders. Read More

    Xeroderma Pigmentosum with Severe Neurological Manifestations/De Sanctis-Cacchione Syndrome and a Novel XPC Mutation.
    Case Rep Med 2017 1;2017:7162737. Epub 2017 Feb 1.
    Unidad de Genetica Médica, Facultad de Medicina, Universidad de Antioquia, Carrera 51D 62-29, Medellín, Colombia.
    Several genetic disorders caused by defective nucleotide excision repair that affect the skin and the nervous system have been described, including Xeroderma Pigmentosum (XP), De Sanctis-Cacchione syndrome (DSC), Cockayne syndrome, and Trichothiodystrophy. Cutaneous photosensitivity with an increased risk of skin malignancy is a common feature of these disorders, but clinical manifestations commonly overlap these syndromes. Several genes have been found to be altered in these pathologies, but we lack more genotype-phenotype correlations in order to make an accurate diagnosis. Read More

    CSB ablation induced apoptosis is mediated by increased endoplasmic reticulum stress response.
    PLoS One 2017 2;12(3):e0172399. Epub 2017 Mar 2.
    Unit of Molecular Genetics of Aging-Department of Ecology and Biology-University of Tuscia, Viterbo, Italy.
    The DNA repair protein Cockayne syndrome group B (CSB) has been recently identified as a promising anticancer target. Suppression, by antisense technology, of this protein causes devastating effects on tumor cells viability, through a massive induction of apoptosis, while being non-toxic to non-transformed cells. To gain insights into the mechanisms underlying the pro-apoptotic effects observed after CSB ablation, global gene expression patterns were determined, to identify genes that were significantly differentially regulated as a function of CSB expression. Read More

    A novel role for transcription-coupled nucleotide excision repair for the in vivo repair of 3,N4-ethenocytosine.
    Nucleic Acids Res 2017 Apr;45(6):3242-3252
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
    Etheno (ε) DNA base adducts are highly mutagenic lesions produced endogenously via reactions with lipid peroxidation (LPO) products. Cancer-promoting conditions, such as inflammation, can induce persistent oxidative stress and increased LPO, resulting in the accumulation of ε-adducts in different tissues. Using a recently described fluorescence multiplexed host cell reactivation assay, we show that a plasmid reporter bearing a site-specific 3,N4-ethenocytosine (εC) causes transcriptional blockage. Read More

    UV-induced proteolysis of RNA polymerase II is mediated by VCP/p97 segregase and timely orchestration by Cockayne syndrome B protein.
    Oncotarget 2017 Feb;8(7):11004-11019
    Department of Radiology, The Ohio State University, Columbus, OH 43210, USA.
    RNA polymerase II (RNAPII) acts as a damage sensor for transcription-coupled nucleotide excision repair (TC-NER) and undergoes proteolytic clearance from damaged chromatin by the ubiquitin-proteasome system (UPS). Here, we report that Valosin-containing protein (VCP)/p97, a druggable oncotarget, is essential for RNAPII's proteolytic clearance in mammalian cells. We show that inhibition of VCP/p97, or siRNA-mediated ablation of VCP/p97 and its cofactors UFD1 and UBXD7 severely impairs ultraviolet radiation (UVR)-induced RNAPII degradation. Read More

    Discrepancy between electroencephalography and hemodynamics in a patient with Cockayne syndrome during general anesthesia.
    J Clin Anesth 2016 Dec 14;35:424-426. Epub 2016 Oct 14.
    Department of Dental Anesthesiology, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address:
    Cockayne syndrome is a kind of progeria with autosomal chromosome recessiveness described first by Cockayne in 1936. Patients with this syndrome were characterized by retarded growth, cerebral atrophy, and mental retardation. We experienced an anesthetic management of a patient with Cockayne syndrome, who underwent dental treatment twice. Read More

    Neurodegeneration in accelerated aging.
    Dan Med J 2016 Nov;63(11)
    The growing proportion of elderly people represents an increasing economic burden, not least because of age-associated diseases that pose a significant cost to the health service. Finding possible interventions to age-associated disorders therefore have wide ranging implications. A number of genetically defined accelerated aging diseases have been characterized that can aid in our understanding of aging. Read More

    Analysis of Drosophila p8 and p52 mutants reveals distinct roles for the maintenance of TFIIH stability and male germ cell differentiation.
    Open Biol 2016 10;6(10)
    Departamento de Genética del Desarrollo, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av Universidad 2001, Cuernavaca Morelos 62250, Mexico
    Eukaryotic gene expression is activated by factors that interact within complex machinery to initiate transcription. An important component of this machinery is the DNA repair/transcription factor TFIIH. Mutations in TFIIH result in three human syndromes: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Read More

    Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA.
    Proc Natl Acad Sci U S A 2016 11 18;113(44):12502-12507. Epub 2016 Oct 18.
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;
    Cockayne syndrome is a neurodegenerative accelerated aging disorder caused by mutations in the CSA or CSB genes. Although the pathogenesis of Cockayne syndrome has remained elusive, recent work implicates mitochondrial dysfunction in the disease progression. Here, we present evidence that loss of CSA or CSB in a neuroblastoma cell line converges on mitochondrial dysfunction caused by defects in ribosomal DNA transcription and activation of the DNA damage sensor poly-ADP ribose polymerase 1 (PARP1). Read More

    Nucleotide excision repair of oxidised genomic DNA is not a source of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine.
    Free Radic Biol Med 2016 10 30;99:385-391. Epub 2016 Aug 30.
    Oxidative Stress Group, University of Leicester, Leicester, United Kingdom; Department of Genetics, University of Leicester, United Kingdom. Electronic address:
    Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is a widely measured biomarker of oxidative stress. It has been commonly assumed to be a product of DNA repair, and therefore reflective of DNA oxidation. However, the source of urinary 8-oxodGuo is not understood, although potential confounding contributions from cell turnover and diet have been ruled out. Read More

    Cockayne syndrome: Clinical features, model systems and pathways.
    Ageing Res Rev 2017 Jan 6;33:3-17. Epub 2016 Aug 6.
    Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA. Electronic address:
    Cockayne syndrome (CS) is a disorder characterized by a variety of clinical features including cachectic dwarfism, severe neurological manifestations including microcephaly and cognitive deficits, pigmentary retinopathy, cataracts, sensorineural deafness, and ambulatory and feeding difficulties, leading to death by 12 years of age on average. It is an autosomal recessive disorder, with a prevalence of approximately 2.5 per million. Read More

    Understanding photodermatoses associated with defective DNA repair: Photosensitive syndromes without associated cancer predisposition.
    J Am Acad Dermatol 2016 Nov;75(5):873-882
    Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. Electronic address:
    Photodermatoses associated with defective DNA repair are a group of photosensitive hereditary skin disorders. In this review, we focus on diseases and syndromes with defective nucleotide excision repair that are not accompanied by an increased risk of cutaneous malignancies despite having photosensitivity. Specifically, the gene mutations and transcription defects, epidemiology, and clinical features of Cockayne syndrome, cerebro-oculo-facial-skeletal syndrome, ultraviolet-sensitive syndrome, and trichothiodystrophy will be discussed. Read More

    Cockayne syndrome: a diffusion tensor imaging and volumetric study.
    Br J Radiol 2016 Nov 19;89(1067):20151033. Epub 2016 Sep 19.
    2 Laboratoire ICube, UMR 7357/FMTS/Université de Strasbourg-CNRS, Strasbourg, France.
    Objective: Cockayne syndrome (CS) is a rare disorder characterized by severe brain atrophy, white matter (WM) hypomyelination and basal ganglia calcifications. This study aimed to quantify atrophy and WM abnormalities using diffusion tensor imaging (DTI) and volumetric analysis, to evaluate possible differences between CS subtypes and to determine whether DTI findings may correspond to a hypomyelinating disorder.

    Methods: 14 patients with CS and 14 controls underwent brain MRI including DTI and a volumetric three-dimensional T weighted sequence. Read More

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