288 results match your criteria pigmentosum neurological

In Silico Drug Repurposing by Structural Alteration after Induced Fit: Discovery of a Candidate Agent for Recovery of Nucleotide Excision Repair in Xeroderma Pigmentosum Group D Mutant (R683W).

Biomedicines 2021 Mar 3;9(3). Epub 2021 Mar 3.

Division of Dermatology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.

Xeroderma pigmentosum complementation group D (XPD) is a UV-sensitive syndrome and a rare incurable genetic disease which is caused by the genetic mutation of the excision repair cross-complementation group 2 gene (). Patients who harbor only XPD R683W mutant protein develop severe photosensitivity and progressive neurological symptoms. Cultured cells derived from patients with XPD (XPD R683W cells) demonstrate a reduced nucleotide excision repair (NER) ability. Read More

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Ocular Features in a Large Cohort of Indians With Xeroderma Pigmentosum.

Cornea 2021 May;40(5):571-577

School of Medical Sciences, University of Hyderabad, Hyderabad, India.

Purpose: Xeroderma pigmentosum (XP) is an extreme hypersensitivity to sunlight causing skin freckling and pigmentary changes because of defective DNA repair mechanisms. The purpose of this article is to evaluate the spectrum of ocular and systemic features in XP at a tertiary eye care center in India over 32 years.

Methods: Data from 418 eyes of 209 patients diagnosed with XP from 1987 to 2018 were reviewed retrospectively for demographics, complaints, ocular features, systemic associations, and their management. Read More

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Transcription blockage by DNA damage in nucleotide excision repair-related neurological dysfunctions.

Semin Cell Dev Biol 2020 Nov 20. Epub 2020 Nov 20.

Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil. Electronic address:

Human genetic syndromes deficient in nucleotide excision repair (NER), such as xeroderma pigmentosum and Cockayne syndrome, may present neurological abnormalities and premature aging symptoms. Unrepaired endogenously generated DNA damage that hampers transcription is a strong candidate that contributes to the development of these severe effects in neuronal tissue. Endogenous lesions include those generated due to byproducts of cellular metabolisms, such as reactive oxygen species. Read More

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November 2020

Molecular analysis directs the prognosis, management and treatment of patients with xeroderma pigmentosum.

DNA Repair (Amst) 2020 09;93:102907

National Xeroderma Pigmentosum Service, Guy's and St Thomas' Foundation Trust, London SE1 9RT, UK.

Xeroderma pigmentosum (XP) is a well-studied disorder of (in most cases) nucleotide excision repair. The establishment in 2010 of a multidisciplinary XP clinic in the UK has enabled us to make a detailed analysis of genotype-phenotype relationships in XP patients and in several instances to make confident prognostic predictions. Splicing mutations in XPA and XPD and a specific amino acid change in XPD are associated with mild phenotypes, and individuals assigned to the XP-F group appear to have reduced pigmentation changes and a lower susceptibility to skin cancer than XPs in other groups. Read More

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September 2020

Autophagy induction on impaired spermatogenesis of xeroderma pigmentosum group A gene-deficient mice.

Biomed Res 2020 ;41(5):237-242

Department of Anatomy, Faculty of Medicine, Tottori University.

Xeroderma pigmentosum (XP) involves a defect in the initial step of nucleotide excision repair (NER) and consists of eight genetic complementation groups (groups A-G and a variant). XP group A (XPA) patients have a high incidence of UV-induced skin tumors, immature testicular development, and neurological symptoms. In an earlier study, we have shown that XP group A (Xpa) gene-knockout mice (Xpa mice) were highly sensitive to UV-induced skin carcinogenesis with a defect in NER and were highly susceptibility to spontaneous tumorigenesis with impaired spermatogenesis. Read More

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January 2020

Novel variants in POLH and TREM2 genes associated with a complex phenotype of xeroderma pigmentosum variant type and early-onset dementia.

Mol Genet Genomic Med 2020 11 16;8(11):e1491. Epub 2020 Sep 16.

Department of Neurosciences, Centro Universitário Saúde ABC, Santo Andre, São Paulo, Brazil.

Background: Xeroderma pigmentosum (XP) is a rare, genetically heterogeneous, autosomal recessive disorder caused by defects in the genes involved in repairing DNA damaged by ultraviolet radiation. These defects lead to a propensity to develop skin cancer at early ages as a hallmark, and progressive neurological degeneration can be observed in around 25% of patients. Eight clinically heterogeneous groups have been identified so far (XPA to XPG and XPV). Read More

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November 2020

A Japanese girl with mild xeroderma pigmentosum group D neurological disease diagnosed using whole-exome sequencing.

Hum Genome Var 2020 7;7:22. Epub 2020 Aug 7.

Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.

We report a Japanese girl with mild xeroderma pigmentosum group D neurological disease. She had short stature, cataracts, intellectual disability, and mild skin symptoms. However, she was not clinically diagnosed. Read More

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XPA deficiency affects the ubiquitin-proteasome system function.

DNA Repair (Amst) 2020 10 16;94:102937. Epub 2020 Jul 16.

Departamento de Biologia Celular e Genética, Universidade Federal do Rio Grande do Norte, CEP 59072-970, Natal, RN, Brazil. Electronic address:

Xeroderma pigmentosum complementation group A (XPA), is defective in xeroderma pigmentosum patients, causing pre-disposition to skin cancer and neurological abnormalities, which is not well understood. Here, we analyzed the XPA-deficient cells transcriptional profile under oxidative stress. The imbalance in of ubiquitin-proteasome system (UPS) gene expression was observed in XPA-deficient cells and the involvement of nuclear factor erythroid 2-related factor-2 (NFE2L2) was indicated. Read More

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October 2020

The past, present, and future of modeling Cockayne Syndrome - A commentary on "Rat Model of Cockayne Syndrome Neurological Disease".

DNA Repair (Amst) 2020 04 28;88:102788. Epub 2020 Jan 28.

Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, and Office of Rare Disease Research, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, United States.

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A novel nonsense mutation of in a Vietnamese family with xeroderma pigmentosum syndrome group D.

Hum Genome Var 2020 10;7. Epub 2020 Feb 10.

Department of Hematology and Dermatology, University Medical Center 3, Ho Chi Minh City, Vietnam.

Xeroderma pigmentosum (XP) group D, a severe disease often typified by extreme sun sensitivity, can be caused by mutations. encodes an adenosine triphosphate (ATP)-dependent DNA helicase, namely XP group D protein (XPD). The XPD, one of ten subunits of the transcription factor TFIIH, plays a critical role in the nucleotide-excision repair (NER) pathway. Read More

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February 2020

ERCC2 mutations in two siblings with a severe trichothiodystrophy phenotype.

J Eur Acad Dermatol Venereol 2020 Apr 6;34(4):876-879. Epub 2020 Jan 6.

Centre for Medical Genetics, Universitair Ziekenhuis Brussel (UZB), Vrije Universiteit Brussel (VUB), Brussels, Belgium.

Background: Trichothiodystrophy (TTD) describes a group of rare genetic disorders of DNA repair, characterized by sulphur-deficient hair, skin anomalies and systemic complications like preterm delivery, neurological impairment, haematological and ophthalmological abnormalities and life-threatening infections.

Objectives: The aim of this case report was to investigate the contribution of the gene mutation to the phenotype.

Methods: We describe the clinical and molecular characteristics of a family with two TTD-affected siblings who died before the age of 2 years. Read More

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Xeroderma Pigmentosum: Ocular Findings in an Isolated Brazilian Group with an Identified Genetic Cluster.

J Ophthalmol 2019 31;2019:4818162. Epub 2019 Oct 31.

Department of Ophthalmology, Federal University of Goias, Goiania, Brazil.

Purpose: Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder characterized by increased susceptibility to UV radiation- (UVR-) induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Eight different genes are affected, and the prevalence of the disease differs across the world. The present study describes the main ophthalmologic features and symptoms in patients with XP in this case series. Read More

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October 2019

Some mutations in the xeroderma pigmentosum D gene may lead to moderate but significant radiosensitivity associated with a delayed radiation-induced ATM nuclear localization.

Int J Radiat Biol 2020 03 26;96(3):394-410. Epub 2019 Nov 26.

Institut National de la Santé et de la Recherche Médicale, UA8 Unit, "Radiations: Defense, Health and Environment" Centre Léon-Bérard, Lyon, France.

Xeroderma Pigmentosum (XP) is a rare, recessive genetic disease associated with photosensitivity, skin cancer proneness, neurological abnormalities and impaired nucleotide excision repair of the UV-induced DNA damage. Less frequently, XP can be associated with sensitivity to ionizing radiation (IR). Here, a complete radiobiological characterization was performed on a panel of fibroblasts derived from XP-group D patients (XPD). Read More

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Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks.

Cell Rep 2019 09;28(12):3167-3181.e6

Cancer Research Center of Toulouse, INSERM, Université de Toulouse, Université Toulouse III Paul Sabatier, CNRS, 31037 Toulouse, France. Electronic address:

Although accumulation of DNA damage and genomic instability in resting cells can cause neurodegenerative disorders, our understanding of how transcription produces DNA double-strand breaks (DSBs) is limited. Transcription-blocking topoisomerase I cleavage complexes (TOP1ccs) are frequent events that prime DSB production in non-replicating cells. Here, we report a mechanism of their formation by showing that they arise from two nearby single-strand breaks (SSBs) on opposing DNA strands: one SSB from the removal of transcription-blocking TOP1ccs by the TDP1 pathway and the other from the cleavage of R-loops by endonucleases, including XPF, XPG, and FEN1. Read More

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September 2019

Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity.

Oxid Med Cell Longev 2019 7;2019:4654206. Epub 2019 Aug 7.

Univ. Grenoble Alpes, SYMMES/CIBEST UMR 5819 UGA-CNRS-CEA, INAC/CEA-Grenoble, Grenoble, France.

The continuous exposure of the human body's cells to radiation and genotoxic stresses leads to the accumulation of DNA lesions. Fortunately, our body has several effective repair mechanisms, among which is nucleotide excision repair (NER), to counteract these lesions. NER includes both global genome repair (GG-NER) and transcription-coupled repair (TC-NER). Read More

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February 2020

Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene-case series.

Neurol Sci 2020 Jan 2;41(1):125-129. Epub 2019 Sep 2.

Genetic Diagnostic Laboratory, Department of Pediatrics and Pediatric Health Center, University of Szeged, Szeged, Korányi fasor 14-15, Szeged, H-6720, Hungary.

Objective: The prevalence of xeroderma pigmentosum (XP) is quite low in Europe, which may result in a delay in determining the appropriate diagnosis. Furthermore, some subtypes of XP, including XPA, may manifest themselves with quite severe neurological symptoms in addition to the characteristic dermatological lesions. Accordingly, the aim of the current study is to highlight the predominant neurological aspects of XPA, as well as mild-to-moderate dermatological signs in a Hungarian family with 5 affected siblings. Read More

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January 2020

Neurogenic bladder associated with xeroderma pigmentosum type A: A case report and literature review.

Urol Case Rep 2019 Nov 20;27:100996. Epub 2019 Aug 20.

Division of Urology, Department of Surgery, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by a defect in deoxyribonucleic acid repair. Along with cutaneous symptoms, neurological symptoms are important clinical features of XP. However, information on neurogenic bladder occurrence among XP cases is rare. Read More

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November 2019

High levels of oxidatively generated DNA damage 8,5'-cyclo-2'-deoxyadenosine accumulate in the brain tissues of xeroderma pigmentosum group A gene-knockout mice.

DNA Repair (Amst) 2019 08 13;80:52-58. Epub 2019 Apr 13.

Medical Genetics Research Center, Nara Medical University, Kashihara, Nara, 634-8521, Japan.

Xeroderma pigmentosum (XP) is a genetic disorder associated with defects in nucleotide excision repair, a pathway that eliminates a wide variety of helix-distorting DNA lesions, including ultraviolet-induced pyrimidine dimers. In addition to skin diseases in sun-exposed areas, approximately 25% of XP patients develop progressive neurological disease, which has been hypothesized to be associated with the accumulation of an oxidatively generated type of DNA damage called purine 8,5'-cyclo-2'-deoxynucleoside (cyclopurine). However, that hypothesis has not been verified. Read More

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[Xeroderma Pigmentosum].

Brain Nerve 2019 Apr;71(4):394-399

Division of Dermatology, Kobe University Graduate School of Medicine.

Xeroderma pigmentosum is a DNA repair disorder characterized by the occurrence of pigmented freckles and skin cancers on sun-exposed areas. Additionally, more than 50% of patients present with progressive degenerative neurological symptoms. Eight clinical subtypes of this condition are known, and neurological symptoms can be seen in XP-A, B, D, F, G complementation groups. Read More

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Heterogeneity and overlaps in nucleotide excision repair disorders.

Clin Genet 2020 01 22;97(1):12-24. Epub 2019 Apr 22.

Istituto di Genetica Molecolare (IGM), Consiglio Nazionale delle Ricerche, Pavia, Italy.

Nucleotide excision repair (NER) is an essential DNA repair pathway devoted to the removal of bulky lesions such as photoproducts induced by the ultraviolet (UV) component of solar radiation. Deficiencies in NER typically result in a group of heterogeneous distinct disorders ranging from the mild UV sensitive syndrome to the cancer-prone xeroderma pigmentosum and the neurodevelopmental/progeroid conditions trichothiodystrophy, Cockayne syndrome and cerebro-oculo-facio-skeletal-syndrome. A complicated genetic scenario underlines these disorders with the same gene linked to different clinical entities as well as different genes associated with the same disease. Read More

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January 2020

Identification of a ERCC5 c.2333T>C (L778P) Variant in Two Tunisian Siblings With Mild Xeroderma Pigmentosum Phenotype.

Front Genet 2019 14;10:111. Epub 2019 Feb 14.

Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis, Tunisia.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder due to a defect in the nucleotide excision repair (NER) DNA repair pathway, characterized by severe sunburn development of freckles, premature skin aging, and susceptibility to develop cancers at an average age of eight. XP is an example of accelerated photo-aging. It is a genetically and clinically heterogeneous disease. Read More

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February 2019

TFIIH: A multi-subunit complex at the cross-roads of transcription and DNA repair.

Adv Protein Chem Struct Biol 2019 10;115:21-67. Epub 2019 Feb 10.

Institut de Génétique et de Biologie Moléculaire et Cellulaire Illkirch Cedex, C.U. Strasbourg, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France; Université de Strasbourg, Illkirch, France. Electronic address:

Transcription factor IIH (TFIIH) is a multiprotein complex involved in both eukaryotic transcription and DNA repair, revealing a tight connection between these two processes. Composed of 10 subunits, it can be resolved into a 7-subunits core complex with the XPB translocase and the XPD helicase, and the 3-subunits kinase complex CAK, which also exists as a free complex with a distinct function. Initially identified as basal transcription factor, TFIIH also participates in transcription regulation and plays a key role in nucleotide excision repair (NER) for opening DNA at damaged sites, lesion verification and recruitment of additional repair factors. Read More

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December 2019

Characteristics of Xeroderma Pigmentosum in Japan: Lessons From Two Clinical Surveys and Measures for Patient Care.

Photochem Photobiol 2019 01 28;95(1):140-153. Epub 2018 Dec 28.

Division of Neurology, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.

Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease caused by deficiency in repair of DNA lesions generated by ultraviolet radiation and other compounds. Patients with XP display pigmentary change and numerous skin cancers in sun-exposed sites, and some patients show exaggerated severe sunburns even upon minimum sun exposure as well as neurological symptoms. We conducted a nationwide survey for XP since 1980. Read More

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January 2019

Macular and Retinal Nerve Fibre Layer Thinning in Xeroderma Pigmentosum: A Cross-sectional Study.

Neuroophthalmology 2018 Dec 22;42(6):356-366. Epub 2018 May 22.

Department of Ophthalmology, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

The purpose of this study was to evaluate retinal thickness in different Xeroderma Pigmentosum (XP) complementation groups using spectral-domain optical coherence tomography (SD-OCT). This was a cross-sectional pilot study of 40 patients with XP. All patients had healthy-looking retinae and optic nerves on slit lamp biomicroscopy, and subtle or no neurological deficits. Read More

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December 2018

Xeroderma pigmentosum: overview of pharmacology and novel therapeutic strategies for neurological symptoms.

Br J Pharmacol 2019 11 23;176(22):4293-4301. Epub 2019 Jan 23.

Ataxia Centre, Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology London, London, UK.

Xeroderma pigmentosum (XP) encompasses a group of rare diseases characterized in most cases by malfunction of nucleotide excision repair (NER), which results in an increased sensitivity to UV radiation in affected individuals. Approximately 25-30% of XP patients present with neurological symptoms, such as sensorineural deafness, mental deterioration and ataxia. Although it is known that dysfunctional DNA repair is the primary pathogenesis in XP, growing evidence suggests that mitochondrial pathophysiology may also occur. Read More

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November 2019

Xeroderma pigmentosum.

Ann Dermatol Venereol 2018 Nov 6;145(11):706-722. Epub 2018 Nov 6.

Service de dermatologie, Hôpital La Rabta, Tunis, Tunisie; Unité de recherche UR 12SP07, Hôpital La Rabta, Tunis, Tunisie. Electronic address:

Xeroderma pigmentosum (XP) is a form of general dermatosis characterised by photo-induced cutaneous-ocular impairment and by skin cancers. In addition to these signs, there may also be neurological involvement. This disease is related to a defect in genes within the nucleotide excision repair system for the first seven genetic groups (A-G), and to an abnormality in transcription groups for the eighth group (xeroderma pigmentosum variant - XPV). Read More

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November 2018

Novel therapeutic approaches to xeroderma pigmentosum.

J L Weon D A Glass

Br J Dermatol 2019 08 25;181(2):249-255. Epub 2018 Nov 25.

Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, U.S.A.

Background: The study of xeroderma pigmentosum has yielded unforeseen advances regarding how defects in the nucleotide excision repair pathway result in this devastating disease, but development of therapeutic strategies has trailed behind the mechanistic discoveries.

Objectives: This review aims to cover clinical presentation, molecular mechanisms and current management, and highlights more recent insights into targeting the deficiencies secondary to the DNA repair defects to prevent skin cancer and/or neurological degeneration.

Methods: This review article discusses novel therapeutic approaches to xeroderma pigmentosum that focus on metabolic defects downstream of nucleotide excision repair. Read More

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Dynamics of DDB2-DDB1 complex under different naturally-occurring mutants in Xeroderma Pigmentosum disease.

Biochim Biophys Acta Gen Subj 2018 12 6;1862(12):2579-2589. Epub 2018 Aug 6.

Biotechnology Center, Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

Background: Xeroderma Pigmentosum (XP) is a disease caused by mutations in the nucleotide excision repair (NER) pathway. Patients with XP exhibit a high propensity to skin cancers and some subtypes of XP can even present neurological impairments. During NER, DDB2 (XPE), in complex with DDB1 (DDB-Complex), performs the DNA lesion recognition. Read More

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December 2018

Clinical features related to xeroderma pigmentosum in a Brazilian patient diagnosed at advanced age.

Appl Clin Genet 2018 10;11:89-92. Epub 2018 Aug 10.

Department of Post Graduate Program in Health Science, São Francisco University, Bragança Paulista, São Paulo, Brazil,

Xeroderma pigmentosum is a rare autosomal recessive genetic disease characterized by extreme sensitivity due to solar radiation and deficiency in excision repair DNA. Those factors promote a set of skin abnormalities such as keratosis, hyperpigmentation, tumors in areas exposed to sunlight, and ocular and, eventually, neurological disorders. In the present review, we summarize the main clinical features related to a case of xeroderma pigmentosum in a man who was not diagnosed until he was 45 years old. Read More

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Neurological manifestations of xeroderma pigmentosum due to gene mutation.

Pract Neurol 2018 12 4;18(6):489-491. Epub 2018 Aug 4.

Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Brazil.

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December 2018