Clinical profile and mutation analysis of xeroderma pigmentosum in Indian patients.

Background: Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by cutaneous and ocular photosensitivity and an increased risk of developing cutaneous neoplasms. Progressive neurological abnormalities develop in a quarter of XP patients. Aim: To study the clinical profile and perform a mutation analysis in Indian patients with xeroderma pigmentosum. Methods: Ten families with 13 patients with XP were referred to our clinic over 2 years. The genes XPA, XPB and XPC were sequentially analyzed till a pathogenic mutation was identified. Results: Homozygous mutations in the XPA gene were seen in patients with moderate to severe mental retardation (6/10 families) but not in those without neurological features. Two unrelated families with a common family name and belonging to the same community from Maharashtra were found to have an identical mutation in the XPA gene, namely c.335_338delTTATinsCATAAGAAA (p.F112SfsX2). Testing of the XPC gene in two families with four affected children led to the identification of the novel mutations c.1243C>T or p.R415X and c.1677C>A or p.Y559X. In two families, mutations could not be identified in XPA, XPB and XPC genes. Limitation: The sample size is small. Conclusion: Indian patients who have neurological abnormalities associated with XP should be screened for mutations in the XPA gene.

Effect of Xeroderma pigmentosum complementation group F polymorphisms and H.pylori infection on the risk of gastric cancer

We conducted a case-control study by genotyping three potential functional SNPs to assess the association of Xeroderma pigmentosum complementation group F [XPF] polymorphisms with gastric cancer susceptibility, and role of XPF polymorphisms in combination with H.pylori infection in the risk of gastric cancer. A hospital case-control study was conducted. A total of 331 patients with gastric cancer and 355 controls were collected. Three SNPs of XPF, XPF rs180067, rs1799801 and rs2276466, were genotyped by Taqman real-time PCR method with a 7900 HT sequence detector system. The gastric cancer patients were more likely to have smoking habit, a family history of cancer and H.pylori infection. We did not find the significant difference in the genotype distributions of XPF rs180067, rs1799801 and rs2276466 between cases and controls. Multivariate logistic analysis showed a non-significant decreased risk in patients carrying rs180067 G allele, rs1799801 T allele or rs2276466 T allele genotypes. The stratification by H.pylori infection was not significantly different in polymorphisms of XPF rs180067, rs1799801 and rs2276466. There was no evidence that polymorphisms in rs180067, rs1799801 and rs2276466 significantly affect the risk of gastric cancer. Further large sample size studies are strongly needed to validate their association

Cockayne syndrome–xeroderma pigmentosum complex with demyelination: A rare association.

Xeroderma pigmentosum–Cockayne syndrome (XP–CS) includes facial freckling and early skin cancers typical of XP and some features typical of CS, such as mental retardation, spasticity, short stature, and hypogonadism. XP–CS does not include skeletal involvement, the facial phenotype of CS, or CNS demyelination and calcifications. We present a rare patient whose genome probably harbored a specific combination of mutations producing a rare double syndrome of XP–CS, with facial phenotype of CS, and CNS demyelination.

Xeroderma pigmentoso: clínica, tratamento e geneterapia / Xeroderma pigmentosum

O xeroderma pigmentoso é uma genodermatose caracterizada por um reparo inadequado de lesões do DNA, ocasionado pela radiação ultravioleta, com conseqüente desenvolvimento de alterações cutâneas, oftálmicas e neurológicas, além de alta incidência de melanomas em crianças. As alterações clínicas são progressivas e aumentam em número em proporção direta à exposição aos raios UV, obrigando os pacientes a estarem totalmente protegidos de qualquer exposição à luz solar. Os autores apresentam o tratamento clínico e as novas e promissoras abordagens terapêuticas e da geneterapia, bem como a classificação clínica dos grupos genéticos.

Xeroderma pigmentosum is a genodermotosis triggered by the inadequate repair of DNA lesions caused by ultraviolet radiation, with the subsequent development of ophthalmic, neurologic, and skin changes, as well as a high incidence of melanoma cases in children. Clinical changes have a progressive pattern, and skin lesions increase in number in the same proportion as UV exposure, forcing patients to protect themselves from any sunlight radiation. Medical treatment, along with the new and promising therapeutic approaches, including gene therapy, are presented in this paper, as well as the clinical classification of the genetic groups.

Xeroderma Pigmentoso: aspectos gerais e apresentaçäo de um caso clínico / Xeroderma pigmentosum: general aspects and presentation of a clinical case

O xeroderma pigmentoso é uma doença causada por um defeito genético que se caracteriza pela perda da capacidade em corrigir defeitos estruturais provocados pelas radiaçöes ultravioletas, que pode levar ao desenvolvimento de câncer cutâneo, alteraçöes oftálmicas, anormalidades neurológicas em idade precoce, além de uma maior freqüência de câncer bucal. Näo há terapêutica específica para a doença, atuando-se principalmente nos aspectos preventivos através da proteçäo contra a luz solar, auto-exame periódico de pele e boca, avaliaçäo clínica com o dermatologista e o estomatologista a cada três meses e tratamento precoce das neoplasias malignas. No caso clínico por nós apresentado, a paciente já era portadora de carcinoma basocelular na face e, no momento atual, notam-se pele senil, lesäo ulcerada na regiäo malar direita e várias lesöes pigmentadas. A semimucosa do lábio inferior apresenta ligeira descamaçäo e lesäo pigmentada, enquanto a mucosa bucal mostra-se com aspecto de normalidade