A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype

Background The nucleotide excision repair (NER) pathway repairs UV‐induced DNA lesions in an accurate fashion and prevents UV‐irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients. Objective Characterization of four new XP‐A patients. Methods Genomic and cDNA sequencing, post‐UV cell survival of living cells, host‐cell reactivation of patients' fibroblasts and Western blotting. Results One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected. Conclusion We discovered four new XP‐A patients and a novel XPA mutation resulting in two diverse patient alleles.