Xeroderma Pigmentosum: Gene Variants and Splice Variants

Martens, Marie Christine; Emmert, Steffen; Boeckmann, Lars

doi:10.3390/genes12081173

Cited by 13 publications

(7 citation statements)

References 53 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…XP can arise from mutations occurring in several factors in the NER pathway, with varying clinical outcomes. These complementation groups vary in severity and rate of occurrence within the population; however, mutations within XPA, XPC, and XPD are most common and account for more than 70% of all XP cases (Cleaver, 2008; Martens et al, 2021).…”

Section: Tfiih Mutations Diseases/disorders and Potential Therapeutic...mentioning

confidence: 99%

“…A number of other XP‐associated mutations have also been found, mainly in the C‐terminal domain of XPD (Table 1). It is generally believed that XP symptoms are correlated with defects in the GG‐NER subpathway (de Laat et al, 1999; Fousteri & Mullenders, 2008; Martens et al, 2021). The global repair deficiency increases UV mutations and higher risk of carcinogenesis in exposed skins cells.…”

Section: Tfiih Mutations Diseases/disorders and Potential Therapeutic...mentioning

confidence: 99%

See 1 more Smart Citation

The role of Transcription Factor IIH complex in nucleotide excision repair

Hoag,

Duan,

Mao

2023

Environ and Mol Mutagen

View full text Add to dashboard Cite

DNA damage occurs throughout life from a variety of sources, and it is imperative to repair damage in a timely manner to maintain genome stability. Thus, DNA repair mechanisms are a fundamental part of life. Nucleotide Excision Repair (NER) plays an important role in the removal of bulky DNA adducts, such as cyclobutane pyrimidine dimers (CPDs) from ultraviolet (UV) light or DNA crosslinking damage from platinum‐based chemotherapeutics, such as cisplatin. A main component for the NER pathway is transcription factor IIH (TFIIH), a multifunctional, 10‐subunit protein complex with crucial roles in both transcription and NER. In transcription, TFIIH is a component of the pre‐initiation complex (PIC) and is important for promoter opening and the phosphorylation of RNA Polymerase II (RNA Pol II). During repair, TFIIH is important for DNA unwinding, recruitment of downstream repair factors, and verification of the bulky lesion. Several different disease states can arise from mutations within subunits of the TFIIH complex. Most strikingly are Xeroderma Pigmentosum (XP), XP combined with Cockayne Syndrome (CS), and Trichothiodystrophy (TTD). Here, we summarize the recruitment and functions of TFIIH in the two NER subpathways, global genomic (GG‐NER) and transcription‐coupled NER (TC‐NER). We will also discuss how TFIIH's roles in the two subpathways lead to different genetic disorders.This article is protected by copyright. All rights reserved.

show abstract

Section: Tfiih Mutations Diseases/disorders and Potential Therapeutic...mentioning

confidence: 99%

Section: Tfiih Mutations Diseases/disorders and Potential Therapeutic...mentioning

confidence: 99%

The role of Transcription Factor IIH complex in nucleotide excision repair

Hoag,

Duan,

Mao

2023

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…pyrimidine 6-4 pyrimidone dimers and cyclobutane pyrimidine dimers) result, which are amendable to DNA repair via the nucleotide excision repair (NER) process. [6][7][8][9][10] NER is capable of removing these nucleic acidbased photoproducts and replacing damaged DNA with new DNA. 11,12 NER is a central pathway safeguarding cells and genomes damaged by UVR.…”

Section: Aetiopathogenesismentioning

confidence: 99%

Xeroderma pigmentosum: an updated review

Leung¹,

Barankin²,

Lam³

et al. 2022

DIC

View full text Add to dashboard Cite

Background: Early recognition of xeroderma pigmentosum is important to minimize the complications arising from the harmful effects of exposure to ultraviolet radiation. This narrative review aims to familiarize physicians with the clinical features, diagnosis and management of xeroderma pigmentosum. Methods:A search was conducted in December 2021 in PubMed Clinical Queries using the key term "xeroderma pigmentosum". The search strategy included all clinical trials, observational studies and reviews published within the past 10 years. The information retrieved from the search was used in the compilation of this article.Results: Xeroderma pigmentosum is a condition of abnormal DNA repair of ultraviolet radiation-induced and oxidative DNA damage, which leads to increased skin cancer susceptibility. Approximately 50% of patients with xeroderma pigmentosum have increased photosensitivity and certain types of xeroderma pigmentosum are more prone to ocular disease and progressive neurodegeneration depending on the causative mutation. The diagnosis should be suspected in patients with increased photosensitivity and characteristic cutaneous, ophthalmological and neurological findings. A definite diagnosis can be made by the identification of biallelic mutation in one of the causative genes. Strict and consistent sun avoidance and protection and early detection and treatment of premalignant and malignant skin lesions are the mainstays of management. Treatment options for actinic keratosis include cryotherapy, topical imiquimod, topical 5-fluorouracil, chemical peeling, excision, CO 2 laser resurfacing, fractional/pulsed laser therapy, and photodynamic therapy. Cutaneous malignancy can be treated by photodynamic therapy, curettage and electrodesiccation, or surgical excision. Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil can be used for the prevention of skin malignancy. Treatment options for poikiloderma include chemical peeling, dermabrasion and laser resurfacing. Methylcellulose eyedrops and soft ultraviolet-protective contact lenses may be used to keep the cornea moist and protect against the harmful effects of keratitis sicca. Investigational therapies include the use of T4 endonuclease-V liposome lotion and oral nicotinamide to reduce the rate of actinic keratoses and non-melanoma skin cancers and gene therapy for radical cure of this condition. Conclusion:Although currently there is no cure for xeroderma pigmentosum, increased awareness and early diagnosis of the condition, followed by rigorous sun avoidance and protection and optimal management, can dramatically improve the quality of life and life expectancy.

show abstract

“…XP is caused by autosomal recessive inheritance of pathogenic variants in nucleotide excision repair (NER) genes, which can be assigned to seven complementation groups —XP-A to XP-G—and one variant form (XPV) [ 38 ]. XP-A is the most affected complementation group, followed by XP-C, representing 30 and 27% of all XP patients, respectively [ 39 ].…”

Section: Syndromes Predisposing To Haematological Malignanciesmentioning

confidence: 99%

Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies—A Review

Filipiuk

Kozakiewicz

Kośmider

et al. 2022

Cancers

View full text Add to dashboard Cite

The view of paediatric cancer as a genetic disease arises as genetic research develops. Germline mutations in cancer predisposition genes have been identified in about 10% of children. Paediatric cancers are characterized by heterogeneity in the types of genetic alterations that drive tumourigenesis. Interactions between germline and somatic mutations are a key determinant of cancer development. In 40% of patients, the family history does not predict the presence of inherited cancer predisposition syndromes and many cases go undetected. Paediatricians should be aware of specific symptoms, which highlight the need of evaluation for cancer syndromes. The quickest possible identification of such syndromes is of key importance, due to the possibility of early detection of neoplasms, followed by presymptomatic genetic testing of relatives, implementation of appropriate clinical procedures (e.g., avoiding radiotherapy), prophylactic surgical resection of organs at risk, or searching for donors of hematopoietic stem cells. Targetable driver mutations and corresponding signalling pathways provide a novel precision medicine strategy.Therefore, there is a need for multi-disciplinary cooperation between a paediatrician, an oncologist, a geneticist, and a psychologist during the surveillance of families with an increased cancer risk. This review aimed to emphasize the role of cancer-predisposition gene diagnostics in the genetic surveillance and medical care in paediatric oncology.

show abstract

Xeroderma Pigmentosum: Gene Variants and Splice Variants

Cited by 13 publications

References 53 publications

The role of Transcription Factor IIH complex in nucleotide excision repair

The role of Transcription Factor IIH complex in nucleotide excision repair

Xeroderma pigmentosum: an updated review

Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies—A Review

Contact Info

Product

Resources

About