Parallel Mining of Gene Expression Differences of Nucleotide Excision Repair Gene XPA in Human Skin Microarrays based on GEO Database / 昆明医科大学学报

Objective To make a parallel mining the data of expression differences of a crucial gene XPA involved in nucleotide excision repair pathway of human skin microarrays by bioinformatics from the system level.Methods Using the ScanGEO, the data of microarrays which included the significant differences expression level of XPA were screened and analyzed from 59 human skin samples in the GEO database. Results There were 7 samples with the down-regulated expression of XPA: cutaneous malignant melanoma, epidermal injury model, DNA damage and UV radiation, foreskin fibroblast response to Toxoplasma gondii RH type 1 (ROP5) mutant infection, interleukin-20 subfamily cytokines effect on epidermal keratinocytes, Egr-1 overexpression effect on skin fibroblasts in vitro: time course, in vitro model for inflammatory dendritic cells.Present expression down. Conclusion Based on the GEO database and ScanGEO, high-throughput shared data can be screened and analyzed efficiently.

Xeroderma pigmentosum group A with mutational hot spot (c.390-1G>C in XPA) in South Korea

PURPOSE: Xeroderma pigmentosum (XP) is rare autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet light is deficient. We reported the first molecularly confirmed Korean patient of XP by targeted exome sequencing. The prevalence of XP included all subtype and carrier frequency of XP-A the using public data were estimated for the first time in South Korea. MATERIALS AND METHODS: We described a 4-year-old Korean girl with clinical diagnosis of XP. We performed targeted exome sequencing in the patient for genetic confirmation considering disease genetic heterogeneity and for differential diagnosis. We verified a carrier frequency of c.390-1G>C in XPA gene known as mutational hot spot using Korean Reference Genome Data Base. We estimated the period prevalence of all subtypes of XP based on claims data of the Health Insurance Review and Assessment Service in South Korea. RESULTS: We identified homozygous splicing mutation of XPA (c.390-1G>C) in the patient. The carrier frequency of risk for XPA (c.390-1G>C) was relatively high 1.608 e-03 (allele count 2/1244). The prevalence of XP in South Korea was 0.3 per million people. CONCLUSION: We expect that c.390-1G>C is hot spot for the mutation of XPA and possible founder variant in South Korea. However, the prevalence in South Korea was extremely low compared with Western countries and Japan.

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.

The relationship between polymorphism of genes XPA, XPC, XPD, XRCC1 and susceptibility to acute lymphoblastic leukemia / 中华内科杂志

ObjectiveTo study the relationship between polymorphism of genes XPA, XPC, XPD,XRCC1 and susceptibility to acute lymphoblastic leukemia (ALL) in a Chinese population.Methods Polymorphism were determined by a case-control study through matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry method of Mass-ASSAY platform in 114 confirmed ALL cases and 169 age- and sex- matched controls, so as to compare the relationship between differert genotypes and ALL risk.ResultsMultivariate logistic regression analysis revealed that individuals carrying at least one 23G variant allele(AG/GG genotypes) had a significantly increased risk for ALL (adjusted OR 2.02; 95％ CI 1.08-3.78) compared with the wild-type genotype (23 AA), and evidence that positive interactions between the polymorphisms in XPC C499T and XPA A23G might occur.Furthermore, individuals with both putative risk genotypes had a significantly higher risk (adjusted OR 5.60; 95％ CI 1.57-19.90), compared with those with both wild-genotypes. By contrast, no significant association was observed between the XPD T751G, XRCC1 G399A, C194T pelymorphism and ALL risk.ConclusionsXPA A23G and XPC C499T polymorphism may contribute to the risk of developing ALL.There are significant combinations between XPC C499T and XPA A23G.