A novel POLH gene mutation in a xeroderma pigmentosum-V Tunisian patient: phenotype-genotype correlation.

XP occurs at higher frequency in Tunisia (1:10,000) than in Japan (1:22,000) (Hirai et al. 2006) and the United States (1 per million) (Kleijer et al. 2008). XP-V cells are unable to synthesize intact daughter DNA strands on UV-irradiated templates resulting from an inability to carry out translesion synthesis (Lehmann et al. 1975; Masutani et al. 1999). Approximately 20% of XP patients belong to XP-V complementation group (Gratchev et al. 2003). In Tunisia, XP is classified into three clinical forms: severe, intermediate with or without neurological abnormalities, and moderate (Zghal et al. 2006). Previous molecular investigation showed homogeneity of mutational spectrum in XPA and XPC genes (Ben Rekaya et al. 2009; Messaoud et al. 2010a,b). The moderate clinical form of XP is characterized by mild dermatological manifestations, no neurological abnormalities and late onset of skin cancers. The median age of onset is 4 years. Mild skin symptoms and late onset of skin tumours have been already described in XP-V (Tanioka et al. 2007), XP-F (Matsumura et al. 1998) and XP-E patients (Rapic-Otrin et al. 2003). Post-UV cell survival in the presence or absence of caffeine (Itoh et al. 2000), unscheduled DNA synthesis (UDS) and detection of polymerase eta employing Western blot (Tanioka et al. 2007) cannot define exactly the molecular defects are in the polymerase eta. These laboratory assays are used to find out the UV sensitivities of the patients’ cells and the DNA repair status of their cells as