Xeroderma pigmentosum, XP, is a rare recessive heterogeneous genetic disorder with an occurence rate of approx. 1 in 250,000 in the U.S.
and 1 in 500,000 in Western Europe . The disorder entails defective UV-radiation damage repair, normally characterized by extreme photosensitivity, pigmentary alterations such as freckles, as well as evident eye damage and skin burning when the epidermal skin layer of the affected individual is exposed to minimal amounts of UV radiation. XP is primarily caused by an autosomal recessive genetic defect in where by nucleotide excision repair (NER) enzymes are mutated, prompting a reduction in or destruction of NER. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die. XP patients have more than a 10,000-fold increased risk of developing skin cancer.
There are 8 XP genes. The first 7 genes (XPA to XPG) relate to nucleotide excision repair (NER), the major mechanism able to fix the DNA damages caused by UV in humans. For example, XPC, an XP gene, encodes a component of NER. It carries out a significant role in the premature steps of global genome NER (GG-NER), predominantly related to damage recognition and repair protein complex, XP-C, formation.