Xeroderma Pigmentosum

Molecular genetics of human malignant melanoma

“…In the latter case, it would appear that some factor(s) that controls the accessibility of active gene regions for preferential repair is perturbed. The presumption of this and other studies [247,248] is that incomplete repair of UVR damage in the DNA from MM patients is qualitatively, but probably not quantitatively, similar to the reduced accessibility case, since the repair enzyme in MM patients is not deficient. Therefore, one part of the puzzle may be that UVR induces DNA damage in epidermal melanocytes that is repaired faultily, repaired too slowly, or not repaired at all.…”

“…Failure to repair this damage can have dire consequences, as is clearly shown in studies of individuals afflicted with the rare inherited disease xeroderma pigmentosum [244,245]. These individuals are homozygous for a recessive mutation that inactivates the gene involved in removal of UVRinduced dimers [246] and, as a result, have a dramatically increased (on the order of lOoo-fold) incidence of skin neoplasms, including basal cell carcinomas and MM [247,248]' Clearly, there is a direct link between simple repair of DNA dimers and prevention of most malignant skin cancers [249]. Therefore, this naturally occurring genetic disorder allows a critical scrutiny of the interplay of specific DNA abnormalities and disease, and has resulted in a number of observations detailing the particular types of faulty repair mechanisms in XP cells, and by analogy to normal epidermal cells.…”

Xeroderma pigmentosum: the role of phototesting

“…There are numerous reports of abnormal reactions to artificial UV radiation in XP. Rothman 2 reported delayed erythema in one patient and Lynch 3 suggested sensitivity from 280 to 310 nm in another patient. The first formal monochromator testing of a patient with XP was performed by Cripps et al .…”

Xeroderma pigmentosum and band-shaped nodular corneal dystrophy.

“…It is now known that the skin of patients with xeroderma pigmentosum is most sensitive to light, having a wavelength of 280 to 310 nm (Lynch, 1934).…”