Xeroderma pigmentosum ( XP ) is a genetic disorder in which there is a decrease in the ability to repair DNA damage as caused by ultraviolet (UV) rays. Symptoms may include severe sunburn after just a few minutes in the sun, spots in sun-exposed areas, dry skin, and skin pigmentation changes. Problems of the nervous system, such as hearing loss, poor coordination, loss of intellectual function, and seizures, may also occur. Complications include a high risk of skin cancer, with about half of skin cancer at age 10 without prevention, and cataracts. Other cancer risks such as brain cancer also occur.
XP is autosomal recessive with at least nine specific mutations can produce conditions. Typically, DNA damage that occurs in skin cells from UV exposure, is corrected by repair of nucleotide excision. In people with xeroderma pigmentosum, this damage is not corrected. As more and more deformities in DNA, cells fail to function and eventually become cancerous or dead. Diagnosis is generally suspected based on symptoms and confirmed by genetic testing.
There is no cure for XP. Treatment involves completely avoiding the sun. These include protective clothing, sunscreen, and dark sunglasses while in the sun. Retinoid cream can help reduce the risk of skin cancer. Vitamin D supplements are generally required. If skin cancer occurs, it is treated in the usual way. Their life expectancy with this condition is about 30 years less than usual.
The disease affects about 1 in 20,000 in Japan, 1 in 250,000 people in the United States, and 1 in 430,000 in Europe. This happens equally commonly in men and women. Xeroderma pigmentosum was first described in the 1870s by Moritz Kaposi. In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristics, pigmented dry skin. Individuals with this disease have been referred to as "night children".
Video Xeroderma pigmentosum
Signs and symptoms
Symptoms include:
- Severe acne when exposed to sunlight in small amounts. This often occurs when the child's first exposure to sunlight.
- Development of multiple spots at an early age
- Gross surface growth (sun keratosis), and skin cancer
- The eyes are very sensitive to the sun and easily become irritated, red and cloudy
- Blistering or freckling on minimum sun exposure
- Telangiectasia (spider veins)
- Hair growth is limited to chest and legs
- Scaly skin
- Xeroderma (dry skin)
- Irregular black spots on skin
- Corneal ulcers
Maps Xeroderma pigmentosum
Genetics
One of the most frequent defects in xeroderma pigmentosum is an autosomal recessive genetic defect in which the nucleotide excision repair enzyme (NER) mutates, leading to NER reduction or elimination. If left unchecked, damage caused by ultraviolet light can cause mutations in individual cell DNA. The cause of neurological disorders is poorly understood and is not associated with exposure to ultraviolet light. Recent theory suggests that oxidative DNA damage is generated during normal metabolism in the central nervous system, and that some of these types of damage should be repaired by APM.
Because DNA repair is under genetic control, it can easily mutate. Many genetic disorders such as xeroderma pigmentosum (XP, MIM 278700) are caused by mutations in genes that repair DNA. If the gene is not corrected properly it can cause xeroderma pigmentosum in the individual. Autosomal recessive disorder xeroderma pigmentosum or XP has a frequency of 1 in every 250,000 people of all races and ethnic groups. Those affected with this autosomal recessive disorder XP are very sensitive to UV rays produced by the sun and even with such short exposure it causes dry skin, peeling and pigmented spots that can develop into skin cancer. Individuals with XP are about 1,000 times more likely to develop skin cancer than uninterrupted individuals.
Molecular defects in XP cells result in very high mutation induction in sun exposed skin from affected individuals. This increased frequency of mutations may cause changes in pigmentation and skin cancer. Examination of mutations in p53 gene in tumors from XP patients showed a p53 mutation of UV exposure characteristic characteristics in most tumors. Like all genetic disorders, genetic counseling and psychological support is right for the family, to discuss possible future pregnancies, feelings of isolation and concern about career prospects. Although there is no cure for xeroderma pigmentosum, the effect can be minimized by obtaining protection from sunlight and if possible early removal of precancerous lesions. The most common fate for individuals with XP is premature death from cancer because they need to take extraordinary steps to protect themselves from the dangers of UV rays. But if no neurological and individual problems are always protected or away from the sun, the prognosis is good.
XP repair protein
The XPA protein acts over NER as a scaffold for the assembly of other DNA repair proteins at the site of DNA damage to ensure proper excision of damage.
The XPB protein (ERCC3) is used in removing double helix DNA after DNA damage is initially recognized. Mutations in the XPB (ERCC3) gene may cause XP or XP to be combined with Cockayne syndrome.
XPC proteins form complexes with RAD23B proteins to form factors of initial damage detection in the improvement of global nucleotide genomic excision (GG-NER). The complex recognizes a wide range of damage that thermodynamically destabilizes duplex DNA.
The XPD (ERCC2) protein, combined with transcription/TFIIH complex repair containing XPB helixase, is used to remove DNA duplex after damage is initially known. Mutations in the XPD (ERCC2) gene cause various syndromes; XP, trichothiodystrophy (TTD), or a combination of XP and Cockayne syndrome (XPCS). Both trichothiodystrophy and Cockayne syndrome display features of premature aging, suggesting a link between poor DNA repair and premature aging (see the theory of DNA damage to aging).
XPE is a heterodimeric protein consisting of two subunits. The larger DDB1 subunit mainly serves as the core component of the CUL4A and CUL4B-based ubiquitin ligase complexes. Substrates that are vaporized by this complex include proteins used in DNA repair.
The XPF (ERCC4) protein along with the ERCC1 protein forms a complex usually called ERCC1-XPF. This complex separates the DNA helices for short distances on both sides of the damage site. Then it acts as an endonuclease to incise a broken DNA strand on the 5 'side of the damaged site. ERCC1-XPF-deficient mutant cells are not only defective in NER, but also in repair of double-strand damage and inter-strand crosslinks.
The XPG protein is the endonuclease that carries DNA over the NER on the 3 'side of the damaged nucleotide. Mutations in the XPG (ERCC5) gene may lead to XP alone, or in combination with Cockayne syndrome (CS), or in combination with deadly serebro-okuli-facio-skeletal syndrome.
Diagnosis
Type
There are seven complementary groups, plus one form of variant:
Treatment
The most obvious and often important part of care is to avoid exposure to sunlight. This includes wearing protective clothing and using sunscreen (physical and chemical). Keratosis can also be treated using cryotherapy or fluorouracil.
Prognosis
Less than 40% of individuals with this disease survive beyond the age of 20 years. Some victims of XP with less severe cases managed to live well until the age of 40s.
History
Xeroderma pigmentosum was first described in 1874 by Hebra and Moritz Kaposi. In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristics, pigmented dry skin.
Popular culture
A CBS television film aired in 1994, Children of the Dark, based on the real life partner Jim and Kim Harrison, whose two daughters own XP.
See also
- Biogerontology
- Cockayne's Syndrome
- List of skin conditions
- List of skin conditions associated with an increased risk of nonmelanoma skin cancer
- Photophobia
- Senescence
References
External links
- GeneReviews/NCBI/NIH/UW entered on xeroderma pigmentosum
Source of the article : Wikipedia
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