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.

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.