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Head and Neck Pathology Jun 2016Xeroderma pigmentosum (XP) is a rare disorder of defective UV-radiation induced damage repair that is characterized by photosensitivity with easy skin burning following... (Review)
Review
Xeroderma pigmentosum (XP) is a rare disorder of defective UV-radiation induced damage repair that is characterized by photosensitivity with easy skin burning following minimal sun exposure, early freckling and development of lentiginous pigmentation along with other features of poikiloderma and a propensity for developing skin cancer at an early age. In this short review, the clinical, pathological, genetic and molecular aspects of XP are reviewed in the current literature. XP encompasses a spectrum of disease that overlaps with other diseases of DNA repair systems. In addition to cutaneous complications, patients are susceptible to eye conditions, neurodegenerative processes, central nervous system tumors and other tumors as a result of UV radiation exposure and its byproducts. Patients with XP frequently experience a shorter life span due to skin cancer and neurodegenerative sequelae, but aggressive preventative measures to minimize UV radiation exposure and damage can improve the course of disease and prolong life. The disease has served as a model for photoaging and UV radiation-induced cancer and has led to a better understanding of cell processes that prevent development of these disease features in normal individuals.
Topics: Humans; Xeroderma Pigmentosum
PubMed: 26975629
DOI: 10.1007/s12105-016-0707-8 -
Cellular and Molecular Life Sciences :... Mar 2022The XPG/ERCC5 endonuclease was originally identified as the causative gene for Xeroderma Pigmentosum complementation group G. Ever since its discovery, in depth... (Review)
Review
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. Here, we provide an overview of the multitasking of XPG in genome maintenance, by describing in detail how its activity in NER is regulated and the evidence that points to important functions outside of NER. Furthermore, we present the various disease phenotypes associated with inherited XPG deficiency and discuss current ideas on how XPG deficiency leads to these different types of disease.
Topics: Animals; DNA Repair; DNA Replication; DNA-Binding Proteins; Endonucleases; Genome; Humans; Nuclear Proteins; Transcription Factors; Xeroderma Pigmentosum
PubMed: 35230528
DOI: 10.1007/s00018-022-04194-5 -
Journal of the College of Physicians... Feb 2011To describe the features of Xeroderma pigmentosum observed in the stage 3 of the disease.
OBJECTIVE
To describe the features of Xeroderma pigmentosum observed in the stage 3 of the disease.
STUDY DESIGN
Case series.
PLACE AND DURATION OF STUDY
Mayo Hospital Lahore, from December 2001 to September 2008.
METHODOLOGY
All patients diagnosed with Xeroderma pigmentosum stage 3 in the outpatient department of the study centre, were included. The age at first presentation, tumour sites, histology, recurrence rate, new tumour formation rate and the number of biopsies taken in a single session were recorded. The follow-up time was seven years.
RESULTS
There were 25 patients including 15 males and 10 females. The mean age at initial presentation with the tumour was 20.4 years. The maximum number of biopsies taken from one patient during the same operation was 15 (mean=4). Complete tumour clearance was achieved in 15 patients and 3 patients were inoperable. Altogether, 70% tumours were basal cell carcinomas (BCC). The average interval for the development of a new tumour was 6 months. Twenty (80%) of the tumours were on the face, one was on the back and 3 on the forearms. Thirteen patients had ocular complications. Fifteen had a first degree relative afflicted. All wounds were closed primarily or with split grafts.
CONCLUSION
There was a family history. The tumours were mostly BCCs. The rate of new tumour formation and recurrence was exceptionally high.
Topics: Adolescent; Adult; Aged; Biopsy; Child; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Pakistan; Xeroderma Pigmentosum
PubMed: 21333240
DOI: No ID Found -
Orphanet Journal of Rare Diseases Nov 2011Xeroderma pigmentosum (XP) is defined by extreme sensitivity to sunlight, resulting in sunburn, pigment changes in the skin and a greatly elevated incidence of skin... (Review)
Review
Xeroderma pigmentosum (XP) is defined by extreme sensitivity to sunlight, resulting in sunburn, pigment changes in the skin and a greatly elevated incidence of skin cancers. It is a rare autosomal recessive disorder and has been found in all continents and racial groups. Estimated incidences vary from 1 in 20, 000 in Japan to 1 in 250, 000 in the USA, and approximately 2.3 per million live births in Western Europe.The first features are either extreme sensitivity to sunlight, triggering severe sunburn, or, in patients who do not show this sun-sensitivity, abnormal lentiginosis (freckle-like pigmentation due to increased numbers of melanocytes) on sun-exposed areas. This is followed by areas of increased or decreased pigmentation, skin aging and multiple skin cancers, if the individuals are not protected from sunlight. A minority of patients show progressive neurological abnormalities. There are eight XP complementation groups, corresponding to eight genes, which, if defective, can result in XP. The products of these genes are involved in the repair of ultraviolet (UV)-induced damage in DNA. Seven of the gene products (XPA through G) are required to remove UV damage from the DNA. The eighth (XPV or DNA polymerase η) is required to replicate DNA containing unrepaired damage. There is wide variability in clinical features both between and within XP groups. Diagnosis is made clinically by the presence, from birth, of an acute and prolonged sunburn response at all exposed sites, unusually early lentiginosis in sun-exposed areas or onset of skin cancers at a young age. The clinical diagnosis is confirmed by cellular tests for defective DNA repair. These features distinguish XP from other photodermatoses such as solar urticaria and polymorphic light eruption, Cockayne Syndrome (no pigmentation changes, different repair defect) and other lentiginoses such as Peutz-Jeghers syndrome, Leopard syndrome and Carney complex (pigmentation not sun-associated), which are inherited in an autosomal dominant fashion. Antenatal diagnosis can be performed by measuring DNA repair or by mutation analysis in CVS cells or in amniocytes. Although there is no cure for XP, the skin effects can be minimised by rigorous protection from sunlight and early removal of pre-cancerous lesions. In the absence of neurological problems and with lifetime protection against sunlight, the prognosis is good. In patients with neurological problems, these are progressive, leading to disabilities and a shortened lifespan.
Topics: DNA Repair; Europe; Humans; Japan; Neoplasms; Nervous System Diseases; United States; Xeroderma Pigmentosum
PubMed: 22044607
DOI: 10.1186/1750-1172-6-70 -
Orphanet Journal of Rare Diseases Apr 2017Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem degenerative disorder (Orpha: 220295; OMIM: 278730, 278760, 278780, 610651). Published... (Review)
Review
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. We also drew on clinical practices used in XP and in Cockayne syndrome without XP to aid management of XP-CS.Extensive searches of the literature identified 43 XP-CS patients. The diagnosis had been confirmed with molecular or biochemical methods in 42 of them. Clinical features of each patient were summarized in spreadsheets and summary statistics were generated from this data. XP patients are classified into complementation groups according to the gene that is mutated. There are four groups in XP-CS, and classification was available for 42 patients. Twenty-one were in the XP-G complementation group, 13 in XP-D, 5 in XP-B, and 3 in XP-F. Overall, the clinical features of XP-CS are very similar to those of CS without XP, with the exception of skin cancers in XP-CS. However, one intriguing finding was that cancer incidence was lower in XP-CS compared to XP alone or XP-neurological disorder. The cancer rate in XP-CS was higher than in CS without XP, an unsurprising finding. There is preliminary evidence for the existence of severity groups in XP-CS, as is the case in CS.Although health problems in XP-CS vary both in severity and in when they the first occur, there was overall homogeneity between all complementation groups and putative severity groups. Severely affected patients met fewer milestones and died at younger ages compared to more mildly affected patients.
Topics: Cockayne Syndrome; Humans; Mutation; Xeroderma Pigmentosum
PubMed: 28376890
DOI: 10.1186/s13023-017-0616-2 -
Genes Jul 2021The nucleotide excision repair (NER) is essential for the repair of ultraviolet (UV)-induced DNA damage, such as cyclobutane pyrimidine dimers (CPDs) and... (Review)
Review
The nucleotide excision repair (NER) is essential for the repair of ultraviolet (UV)-induced DNA damage, such as cyclobutane pyrimidine dimers (CPDs) and 6,4-pyrimidine-pyrimidone dimers (6,4-PPs). Alterations in genes of the NER can lead to DNA damage repair disorders such as Xeroderma pigmentosum (XP). XP is a rare autosomal recessive genetic disorder associated with UV-sensitivity and early onset of skin cancer. Recently, extensive research has been conducted on the functional relevance of splice variants and their relation to cancer. Here, we focus on the functional relevance of alternative splice variants of XP genes.
Topics: DNA Damage; DNA Repair; Humans; Mutation; Pyrimidine Dimers; RNA Splicing; Xeroderma Pigmentosum
PubMed: 34440347
DOI: 10.3390/genes12081173 -
BMJ (Clinical Research Ed.) Feb 2008Alex Webb was 4 years old when he was diagnosed with xeroderma pigmentosum nine years ago. This is his story as told by his mother. His parents established a support... (Review)
Review
Alex Webb was 4 years old when he was diagnosed with xeroderma pigmentosum nine years ago. This is his story as told by his mother. His parents established a support group that is now widely recommended by consultant dermatologists
Topics: Anecdotes as Topic; Humans; Internet; Male; Social Support; Social Work; Xeroderma Pigmentosum
PubMed: 18292171
DOI: 10.1136/bmj.39485.698356.AD -
Revista Paulista de Pediatria : Orgao... 2023The aim of this study was to describe the disease and treatment and to alert health professionals for the identification of signs and symptoms and the need for an early...
OBJECTIVE
The aim of this study was to describe the disease and treatment and to alert health professionals for the identification of signs and symptoms and the need for an early diagnosis in patients with xeroderma pigmentosum (XP).
CASE DESCRIPTION
An 8-year-old male patient was referred to the Joana de Gusmão Hospital (HIJG) in 2021 for evaluation and specialized care. Previously, the child was followed in his place of origin by oncologic and palliative care, where he was submitted to surgeries and chemotherapy. He was admitted to the HIJG using vismodegib, acitrein, tramadol, and solar protective measures. On physical examination, there were tumors and disseminated macular verrucous and ulcerated lesions. The imaging examination showed solid and expansive lesions on the face, and atelectasis and fibroscarring changes in the lung. The histopathological report proved the existence of melanocanthoma, carcinoma, and pyogenic granuloma. After the evaluation of the case, no surgery, chemotherapy, or radiotherapy was performed. It was decided to maintain the palliative treatment and to continue the use of tramadol for pain, and vismodegib and acitretin were used to control carcinomas and prophylactic measures.
COMMENTS
The XP is a rare disease of autosomal recessive inheritance whose mechanism comes from failure in the DNA repair by exposure to ultraviolet rays, resulting in lesions on the skin and mucous membranes. They start as sunburns and can progress to melanosis, areas with altered pigmentation, premature aging, poikiloderma, and areas of high risk for neoplasms.
Topics: Child; Male; Humans; Xeroderma Pigmentosum; Tramadol; DNA Repair; Skin Diseases; Carcinoma; Skin Neoplasms
PubMed: 36921168
DOI: 10.1590/1984-0462/2023/41/2021390 -
The Indian Journal of Medical Research Nov 2020
Topics: Cockayne Syndrome; DNA Repair; Humans; Rare Diseases; Xeroderma Pigmentosum
PubMed: 35345132
DOI: 10.4103/ijmr.IJMR_2097_19 -
Brain : a Journal of Neurology Dec 2023Xeroderma pigmentosum (XP) results from biallelic mutations in any of eight genes involved in DNA repair systems, thus defining eight different genotypes (XPA, XPB, XPC,...
Xeroderma pigmentosum (XP) results from biallelic mutations in any of eight genes involved in DNA repair systems, thus defining eight different genotypes (XPA, XPB, XPC, XPD, XPE, XPF, XPG and XP variant or XPV). In addition to cutaneous and ophthalmological features, some patients present with XP neurological disease. It is unknown whether the different neurological signs and their progression differ among groups. Therefore, we aim to characterize the XP neurological disease and its evolution in the heterogeneous UK XP cohort. Patients with XP were followed in the UK National XP Service, from 2009 to 2021. Age of onset for different events was recorded. Cerebellar ataxia and additional neurological signs and symptoms were rated with the Scale for the Assessment and Rating of Ataxia (SARA), the Inventory of Non-Ataxia Signs (INAS) and the Activities of Daily Living questionnaire (ADL). Patients' mutations received scores based on their predicted effects. Data from available ancillary tests were collected. Ninety-three XP patients were recruited. Thirty-six (38.7%) reported neurological symptoms, especially in the XPA, XPD and XPG groups, with early-onset and late-onset forms, and typically appearing after cutaneous and ophthalmological symptoms. XPA, XPD and XPG patients showed higher SARA scores compared to XPC, XPE and XPV. SARA total scores significantly increased over time in XPD (0.91 points/year, 95% confidence interval: 0.61, 1.21) and XPA (0.63 points/year, 95% confidence interval: 0.38, 0.89). Hyporeflexia, hypopallesthaesia, upper motor neuron signs, chorea, dystonia, oculomotor signs and cognitive impairment were frequent findings in XPA, XPD and XPG. Cerebellar and global brain atrophy, axonal sensory and sensorimotor neuropathies, and sensorineural hearing loss were common findings in patients. Some XPC, XPE and XPV cases presented with abnormalities on examination and/or ancillary tests, suggesting underlying neurological involvement. More severe mutations were associated with a faster progression in SARA total score in XPA (0.40 points/year per 1-unit increase in severity score) and XPD (0.60 points/year per 1-unit increase), and in ADL total score in XPA (0.35 points/year per 1-unit increase). Symptomatic and asymptomatic forms of neurological disease are frequent in XP patients, and neurological symptoms can be an important cause of disability. Typically, the neurological disease will be preceded by cutaneous and ophthalmological features, and these should be actively searched in patients with idiopathic late-onset neurological syndromes. Scales assessing cerebellar function, especially walking and speech, and disability can show progression in some of the groups. Mutation severity can be used as a prognostic biomarker for stratification purposes in clinical trials.
Topics: Humans; Xeroderma Pigmentosum; Activities of Daily Living; Prospective Studies; DNA Repair; Mutation; Central Nervous System Diseases
PubMed: 38040034
DOI: 10.1093/brain/awad266