Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cytogenetic observation, that the sister chromatid exchanges (SCE) occur 3 times more frequently in a special form of xeroderma pigmentosum--XPII than in the norm, prompted a study of DNA replication in this rare disease. Using DNA fiber autoradiography, the rate of fork movement and the frequency of initiation in the adjacent clusters of replicons were estimated. The rate of fork movement was significantly slower than that in classical XP and in normal cells. Here evidence was provided on another defect in DNA replication in XPII that involves a significantly decreased number of simultaneously operating adjacent clusters of replicons, which results in a decreased rate of DNA chain-growth. According to the Painter replication model for SCE, the exchanges arise due to double-strand DNA breaks occurring on the border between two adjacent clusters, respectively, completely and partially replicated. A retarded fork-displacement rate together with a decreased rate of DNA-chain growth may cause this situation to persist longer than in the norm. Thus, our data provide a further support of the replication model for SCE. A similar combination of cytogenetic and molecular defects has been obtained earlier in the Bloom syndrome cells.
 ...
PMID:[The interrelation between changes in the structural organization of replicon clusters, a retarded fork displacement rate and the high level of spontaneous SCEs in form II of xeroderma pigmentosum]. 145 62

Since all organisms are continuously exposed to exogenous and endogenous DNA damaging agents, mechanisms of repair of DNA lesions are necessary to maintain the integrity of the genome. Studies of the cellular defects in human inherited diseases with deficiencies in DNA repair have given new insights into these processes. Nucleotide excision repair is an important DNA repair pathway in which several types of DNA lesions are removed by a multi-step enzymatic process. This repair mechanism is deficient in the rare disease xeroderma pigmentosum (XP), which results in extreme sensitivity to ultraviolet light (UV) and development of UV-induced skin tumors at an early age. There are several genetic complementation groups of XP. The genes that are mutated in some of the XP complementation groups have been cloned and the functions of the encoded proteins are being characterised. Several types of DNA lesions are removed more rapidly from active genes than from other regions of DNA. This preferential repair of active genes is deficient in Cockayne's syndrome, which is characterised by developmental abnormalities and UV-sensitivity but no marked increase in cancer incidence. Other syndromes associated with increased sensitivity to certain DNA damaging agents where no defect in DNA repair has been defined include Fanconi's anemia (sensitivity to DNA cross-linking agents), hereditary dysplastic nevus syndrome (sensitivity to UV) and ataxia-telangiectasia (sensitivity to ionizing radiation).
 ...
PMID:Inherited defects in DNA repair and susceptibility to DNA-damaging agents. 147 Nov 67

Xeroderma pigmentosum is a very rare disease caused by an inherited defect in the DNA repair system. The cells are less able to repair defects caused by UV radiation, which results in early aging of the skin and the development of malignant skin tumors. Robins assumes that the eye is involved in 60% of the cases. In our patient we found a dense opacity of both corneas in addition to the typical lentiginous alteration of the skin. Therefore, a corneal transplantation was carried out on both eyes. The corneal buttons obtained by keratoplasty were examined by light, and transmission electron microscopy. We found massive alterations in the tissues of all corneal layers.
 ...
PMID:[Ultrastructural findings in the cornea in xeroderma pigmentosum]. 275 27

There are numerous risk factors for the development of malignant melanoma. It has been documented that genetic predisposition exists but exogenous factors are also very important. In familial melanomas it has been well established that mutation in the CDKN2A gene which is located at chromosome 9 leads to a marked risk for malignant melanoma. This tumor-suppressor gene is important for the regulation of the cell cycle and mutation in this gene is associated also with an increased rate of pancreas cancer. The penetrance of this mutation is influenced by UV-energy. In addition it has been shown that a second cluster for the familial atypical nevus syndrome is located at chromosome 1p36. Patients with the rare disease xeroderma pigmentosum have a defect in the DNA-repair mechanism inherited in an autosomal recessive trait and therefore develop within the first 20 years of life numerous malignant skin tumours including malignant melanomas. But also in non-syndromic patients a decrease of DNA-repair ability may occur. It has been shown recently that reduced DNA-repair ability is an independent risk factor for malignant melanoma and may contribute to susceptibility to sunlight-induced melanoma among the general population. Other constitutional risk factors for the development of malignant melanoma are fair skin, red hair and blue eyes. The most important exogenous risk factor is UV-exposition. Extensive and repetitive sunburns before the age of 15 years are especially predisposing to malignant melanoma. The most important preventive measures are continuous sun-protection including avoidance of sun in noon time on tropical and subtropical places, wearing a hut and sunglasses and application of sun-screens with high sun-protection factor. Furthermore a regular check for changing moles is indicated in persons with multiple atypical nevi or a familial melanoma syndrome. Nowadays molecular genetic screenings are available within research projects for members of melanoma-prone families. The controversy of such possibilities is discussed.
 ...
PMID:[Genetic counseling and DNA testing in patients with increased risks for malignant melanoma]. 1450 54

The past two decades of research into Xeroderma pigmentosum (XP), an autosomal recessive disease, has been marked by significant progress in understanding the molecular basis of this rare disease. More importantly, especially from the perspective of the affected families, is that this knowledge has been applied to diagnose the condition both in utero as well as in the very early days of life. The eight known XP genes and their different phenotypes present a number of challenges that the XP Workshop sponsored by the NIH in 2010 has highlighted. There is little current treatment specifically designed for any of the XP types other than standard dermatological and neurological evaluations and care. The Xeroderma Pigmentosum Family Support Group (XPFSG) is dedicated to serving families with children and adults with all forms of XP and to help them better understand the condition, to identify practical measures which can be taken by the XP patients and their families to mitigate the effects of the disease, and to serve as patient advocates to help families discuss issues with their physicians. We summarize our efforts in terms of outreach within the US and abroad to affected families and discuss XPFSG-sponsored clinical initiatives that include molecular diagnoses, treatment, and initial proof-of-concept studies that can, if successful, improve the lives of XP patients in the near term.
 ...
PMID:Xeroderma pigmentosum family support group: Helping families and promoting clinical initiatives. 2157 Sep 26

Skin melanoma is an extremely rare disease at pediatric age and its incidence increases with age. Links with predisposition syndrome exists (giant congenital naevus, xeroderma pigmentosum). Diagnosis is often difficult and distinction between benign or malignant lesion is sometime impossible (Spitzoid naevus, melanocytic neoplasms) leading to the diagnosis of "melanocytic tumor of uncertain malignant potential" (MELTUMP). Atypical features (amelanotic or raised lesions, atypical histotype) are frequent leading to delay in treatment. Diagnosis and treatment require expertise for pathologists and dermatologists pediatricians. Invasive melanomas are of poor prognosis despite recent progress in adult treatment. Early and rigorous treatment of suspect skin lesions is necessary.
 ...
PMID:[Melanoma in children: diagnosis and treatment specificities]. 2296 89