Xeroderma pigmentosum is an inherited disease caused by defective repair mechanisms of DNA repair during cell division. These defects lead to increased light sensitivity (photosensitivity) of the skin to UV rays, premature skin aging and an extremely increased risk of skin cancer at a young age. In addition, diseases of the nervous system and the eyes can occur.
Epidemiology
Xeroderma pigmentosum is very rare. Worldwide the frequency is about 1:1. 000.
000, but in Europe it is 1:125. 000, in Japan even 1:40. 000. Most patients come from Japan, Germany, North Africa, North America and Turkey. Men and women are equally affected.
History
Xeroderma pigmentosum was first described in 1870 by Ferdinand von Hebra (1816-1880), Austrian dermatologist from Vienna, and Moritz Kaposi (1837-1902), Hungarian dermatologist also from Vienna. They referred to XP in the “Textbook of Skin Diseases” published in 1870 as xeroderma or parchment skin and defined it as a loss of tissue (atrophy) of the skin. In 1882, Kaposi referred to the pigment abnormalities as an important symptom in a publication and therefore gave this disease the name Xeroderma pigmentosum.
Albert Neisser (1855-1916), a German dermatologist, was the first to discover in 1883 that neurological diseases were also associated with Xeroderma pigmentosum. A few years after Neisser’s discovery, Charles Louis Xavier Arnozan (1852-1928), a French physician, recognized the damaging influence of light and air on the course of Xeroderma pigmentosum. In 1969, J. E. Cleaver discovered the cause of Xeroderma pigmentosum and thus took the first step towards understanding the central role of DNA mutations in cancer. As a result, the disease has gained a special place in the history of medicine.
Causes of Xeroderma pigmentosum
Xeroderma pigmentosum is a hereditary disease that is inherited autosomal recessively, i.e. two defective genes must come together, i.e. both parents must carry the defective gene in order for the disease to break out. Exposure to sunlight, UVB radiation more than UVA radiation, leads to changes in the DNA located in cells exposed to the sun.
Particularly often, a duplication of a building block of DNA, the base thymine, occurs, so that the new DNA strand is functionally inactivated. Normally, the cell has repair mechanisms that correct the error. In Xeroderma pigmentosum, however, these mechanisms are reduced or defective.
There are seven different types of XP, which are subdivided according to the location of the gene defect (A-G), and one variant with different gene defects: In the XP groups A-G, a mechanism is diminished or defective that cuts the second thymine base from the DNA strand and replaces it with the correct base (excision mechanism). Therefore, the double thymine bases are retained (thymine dimers) and are then completely excised by a defective emergency mechanism, which leads to a mutation of the DNA strand and thus to a mutation of the body. This leads to an accumulation of DNA damage and mutations caused by UV rays, drugs or even free radicals.
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