In addition, we show that in the absence of UV, XP-C keratinocytes exhibit intrinsic cell cycle abnormalities, and β 1-integrin overexpression, defects that are also both fully reversed after genetic correction. In this study, we demonstrate that DNA repair capacity, cell survival properties, and transition from proliferative to abortive keratinocyte colonies toward UVB irradiation can be fully recovered in keratinocytes from patients with XPC transduced with a retroviral vector stably driving the expression of the wild-type XPC protein.
#Xeroderma pigmentosum pdf skin
This has prompted us to undertake genetic correction of XP-C fibroblasts and particularly keratinocytes, which are the most relevant cells in relation to skin cancer and have proven recently to be capable of reconstructing XP-C skin in vitro.
#Xeroderma pigmentosum pdf free
Among the seven classic XP complementation groups known to date (XP-A to XP-G), XP-C is the most common one in Europe and North Africa and XP-C patients remain free of neurologic problems often seen in other XP complementation groups. Cells from patients with classic XP are deficient in nucleotide excision repair, a versatile biochemical mechanism for removal of ultraviolet-induced DNA lesions. Most cancers developed by XP patients are basal and squamous cell carcinoma strikingly restricted to sun-exposed parts of the skin. Sun-exposed areas of the tongue may develop abnormal keratinization and vascularization (telangiectasias) ( Figure 1e).Xeroderma pigmentosum (XP) is a rare photosensitive and cancer-prone syndrome transmitted as an autosomal recessive trait. Similarly, damage to the epithelial cells of the lips leads to dryness, scaling, and inflammation (cheilitis). As damage progresses, these lesions may become premalignant and develop into melanoma in the general population and more rapidly in patients with XP ( Figure 1d). As damage accumulates, photoaged skin develops lentigos ( Figure 1a and c)-pigmented lesions of varying size, color, and irregular borders that are distributed unevenly across the skin. Freckling is a common finding in children with XP under the age of 2 years and is rarely seen in children at this age in the general population. Abbreviations: BCC ( basal cell carcinoma), BER ( base excision repair), CPD ( cyclobutane pyrimidine dimer), CPU ( cyclosporine deoxynucleoside), CS ( Cockayne syndrome), DDT ( DNA damage tolerance), DSB ( double-strand break), GG-NER ( global genome nucleotide excision repair), NER ( nucleotide excision repair), NIH ( National Institutes of Health), PND ( progressive neurodegeneration), POI ( premature ovarian insufficiency), PP ( photoproduct), SC ( stem cell), SCC ( squamous cell carcinoma), SSB ( single-strand break), TBUT ( tear film break up time), TC-NER ( transcription-coupled nucleotide excision repair), US ( United States), XP ( xeroderma pigmentosum), XPV ( xeroderma pigmentosum variant)ĭamage to melanocytes leads to pigmentary changes from mild (freckles) to severe (severe dysplasia and/or melanoma). XP is a unique model of human premature aging, which is revealing new insights into aging mechanisms. Taken together, these clinical findings highlight the importance of DNA repair in maintaining genomic integrity. Premature ovarian failure is overrepresented among females with XP, occurring 20 years earlier than in the general population. Internal malignancies, such as lung cancer, CNS tumors, and leukemia and/or lymphoma, occur at a younger age in patients with XP, as do thyroid nodules. Internal manifestations of premature aging, including peripheral neuropathy, progressive sensorineural hearing loss, and neurodegeneration, are reported in 25% of patients with XP. Patients with XP also exhibit ocular changes secondary to premature photoaging, including ocular surface tumors and pterygium. Poikiloderma, atypical lentigines, and skin cancers, the primary cutaneous features of XP, occur in the general population but at a much older age.
Inherited diseases of DNA repair, such as xeroderma pigmentosum (XP), provide an excellent model for human aging due to the accelerated accumulation of DNA damage.
The skin is ideal to visually differentiate their unique features. Journal of Investigative Dermatology Symposium ProceedingsĪging results from intrinsic changes (chronologic) and damage from external exposures (extrinsic) on the human body.Resources for Clinical Research in the JID.Montagna Symposium on the Biology of Skin.
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