Xeroderma Pigmentosum

From DNA Repair Lab

Xeroderma pigmentosum (XP) is a rare genetic disease characterized mainly by high increased incidence of skin cancer and extremely sensibility to sunlight. The XP carries are not able to fix the damages caused at DNA by the ultraviolet (UV) component of the sunlight. These lesions in the genetic material of the XP patients can kill the cells or generate mutations that accumulate at DNA, eventually leading to cancer.

In the case of this syndrome, the incidence of skin cancer is raised approximately thousand times, when compared to normal people. Due to the absence of cure or effective treatment, as well as the accumulation of mutations and consequent worst of symptoms, the best way to avoid premature skin cancer is to avoid exposition to sun light or any another source of UV light, like some fluorescent lamps, since their early infancy. For this reason these kids are normally referred as “the children of the moon”.

Other symptoms may also occur in some XP patients. The most usual are:

• blistering or freckling on minimum sun exposure;

• premature aging of sun exposed areas;

• blindness resulting from eye lesions or surgery for skin cancer close to the eyes;

• progressive neurological complications including: mental retardation, developmental disabilities, high frequency hearing loss, progressing to deafness.

There were identified eight XP genes. The seven first genes (XPA to XPG) are related with the nucleotide excision repair (NER), that is the major mechanism able to fix the DNA damages caused by UV in humans. Some patients have mutation in the gene XPV (XP variant), which encode for a translesion DNA polymerase.

Interesting link for the American XP Society: www.xps.org

More information can be found at:

Menck, CFM, Armelini, MG and Lima-Bessa, KM (2007) On the search for skin gene therapy strategies of xeroderma pigmentosum disease. Current Gene Therapy, 7(3): 163-174.

Costa RM, Chiganças V, Galhardo RS, Carvalho H, Menck CF (2003) The eukaryotic nucleotide excision repair pathway Biochimie 85: 1083-1099.