Xeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient. This disorder leads to multiple basaliomas and other skin malignancies at a young age. In severe cases, it is necessary to avoid sunlight completely. The two most common causes of death for XP victims are metastatic malignant melanoma and squamous cell carcinoma^[1]. XP is about six times more common in Japanese people^[1] than in other groups.

Cause

PAGENAME has an autosomal recessive pattern of inheritance.

The most common defect in xeroderma pigmentosum is a genetic defect whereby nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER.^[2] Unrepaired damage can lead to mutations, altering the information of the DNA in individual cells. If mutations affect important genes, like tumour suppressor genes (e.g. p53) or proto oncogenes then this disorder may lead to cancer. Patients exhibit elevated risk of developing cancer, such as basal cell carcinoma.

Normally, damage to DNA in epidermal cells occurs during exposure to UV light. The absorption of the high energy light leads to the formation of pyrimidine dimers, namely CPD's (cyclobutane-pyrimidine-dimers) and 6-4PP's (pyrimidine-6-4-pyrimidone photoproducts). The normal repair process entails nucleotide excision. The damage is excised by endonucleases, then the gap is filled by a DNA polymerase and "sealed" by a ligase.

Types

There are 7 complementation groups, plus one variant form :

|- 
|Type  A, I, XPA

|- 
|Type B, II, XPB

|-
|Type C, III, XPC

|- 
|Type D, IV, XPD

|- 
|Type E, V, XPE

|- 
|Type F, VI, XPF

|- 
|Type G, VII, XPG

|-
|Type V, XPV 

Symptoms

Some of the most common symptoms of XP include:

• An unusually severe sunburn after a short sun exposure. The sunburn may last for several weeks. The sunburn usually occurs during a child's first sun exposure.
• Development of many freckles at an early age .
• Irregular dark spots on the skin .
• Thin skin .
• Excessive dryness of skin .
• Rough-surfaced growths (solar keratoses), and skin cancers .
• Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot, and clouded, .
• Blistering or freckling on minimum sun exposure.
• Premature aging of skin, lips, eyes, mouth and tongue.
• Crusting skin
• Spidery blood vessels
• Scaly skin
• Oozing raw skin surface
• Limited growth of hair on chest and legs.

Treatment

The most important part of managing the condition is reducing exposure to the sun. The number of keratoses can be reduced with Isotretinoin (http://www.emedicine.com/DERM/topic462.htm#section~treatment) (though there are significant side-effects.) Existing keratoses can be treated using cryotherapy or fluorouracil.

In Popular Culture

Christopher Snow, the protagonist and narrator of Dean Koontz' Moonlight Bay Trilogy of novels (Fear Nothing, Seize The Night and the to-be-completed Ride The Storm), has severe enough XP that he must avoid sunlight and as much artificial light as possible at all costs, living his life at night and then only by dim bulbs and candlelight, though always maintaining a positive and envigorated attitude about life, even authoring a best-selling autobiographical book on living with XP.

Alejandro Amenábar's Award-winning film, The Others, centers around a woman (Nicole Kidman) whose children suffer from XP and must be kept indoors, behind closed curtains, at all times.

Yui stars in a romantic Japanese movie Taiy? no Uta, where she plays the lead character, a street musician named Kaoru Amane, who is diagnosed with Xeroderma Pigmentosum and only performs at night because of this disease. Even with this diagnosis, she chases her dreams of becoming a singer and meets K?ji Fujishiro (Takashi Tsukamoto), who also has a passion for music and whom Kaoru eventually falls in love with. This story was also the basis for a Japanese TV drama series, also called "Taiy? no Uta", starring Erika Sawajiri and Takayuki Yamada in the roles of Kaoru and K?ji.

References

See also

• Biogerontology
• Cockayne syndrome
• Photophobia
• Senescence
• XPB

External links

• Sloan Science and Film / Short Films / XP by David Barba 10 minutes
• XP Society
• XP Family Support Group
• UK Patient Support Group
• An article about this disorder in English and Italian
• Web Site of a Short Film about an Xeroderma pigmentosum (XP) Patient. Film is directed by Kimberly Williams Paisley
• Article About the Xeroderma pigmentosum (XP) Society by William Lambers (pdf format)

bg:?????????? ca:Xerodčrmia pigmentada da:Xeroderma pigmentosum de:Xeroderma pigmentosum es:Xerodermia pigmentosa fr:Xeroderma pigmentosum id:Xeroderma pigmentosum it:Xeroderma pigmentoso he:???????? ?????????? nl:Xeroderma pigmentosum ja:?????? pl:Skóra pergaminowa pt:Xerodermia pigmentosa ru:?????????? sr:?????????? ??????????? zh:??????