Xeroderma pigmentosum: Difference between revisions
Geofreeman32 (talk | contribs) No edit summary |
No edit summary |
||
Line 87: | Line 87: | ||
==See also== |
==See also== |
||
*[[hey whats up]] |
|||
*[[Biogerontology]] |
*[[Biogerontology]] |
||
*[[Cockayne syndrome]] |
*[[Cockayne syndrome]] |
Revision as of 20:27, 9 February 2012
Xeroderma pigmentosum | |
---|---|
Specialty | Medical genetics |
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.[1]: 574 In extreme cases, all exposure to sunlight must be forbidden, no matter how small. Multiple basal cell carcinomas (basaliomas) and other skin malignancies frequently occur at a young age in those with XP. In fact, metastatic malignant melanoma and squamous cell carcinoma[2] are the two most common causes of death in XP victims. This disease involves both sexes and all races, with an incidence of 1:250,000 and a gene frequency of 1:200. XP is roughly six times more common in Japanese people[2] than in other groups.
The most common defect in xeroderma pigmentosum is an autosomal recessive genetic defect in which nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER.[3] If left unchecked, damage caused by ultraviolet (UV) light can cause mutations in individual cell's DNA. If tumor suppressor genes (e.g. p53) or proto oncogenes are affected, the result may be cancer. Patients with XP are at a high risk for developing skin cancers, such as basal cell carcinoma, for this reason.
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 cyclobutane-pyrimidine dimers and pyrimidine-6-4-pyrimidone photoproducts. In a healthy, normal human being, the damage is first excised by endonucleases. DNA polymerase then repairs the missing sequence, and ligase "seals" the transaction. This process is known as nucleotide excision repair.
Types
There are seven complementation groups, plus one variant form:
Type | Diseases Database | OMIM | Gene | Locus | Also known as/Description |
Type A, I, XPA | Template:DiseasesDB2 | Template:OMIM2 | XPA | 9q22.3 | Xeroderma pigmentosum group A - the classical form of XP |
Type B, II, XPB | Template:DiseasesDB2 | Template:OMIM2 | XPB | 2q21 | Xeroderma pigmentosum group B |
Type C, III, XPC | Template:DiseasesDB2 | Template:OMIM2 | XPC | 3p25 | Xeroderma pigmentosum group C |
Type D, IV, XPD | Template:DiseasesDB2 | Template:OMIM2 Template:OMIM2 | XPD ERCC6 | 19q13.2-q13.3 , 10q11 | Xeroderma pigmentosum group D or De Sanctis-Cacchione syndrome (can be considered a subtype of XPD) |
Type E, V, XPE | Template:DiseasesDB2 | Template:OMIM2 | DDB2 | 11p12-p11 | Xeroderma pigmentosum group E |
Type F, VI, XPF | Template:DiseasesDB2 | Template:OMIM2 | ERCC4 | 16p13.3-p13.13 | Xeroderma pigmentosum group F |
Type G, VII, XPG | Template:DiseasesDB2 | Template:OMIM2 Template:OMIM2 | RAD2 ERCC5 | 13q33 | Xeroderma pigmentosum group G and COFS syndrome type 3 |
Type V, XPV | Template:OMIM2 | POLH | 6p21.1-p12 | Xeroderma pigmentosum variant - these patients suffer from mutation in a gene that codes for a specialized DNA polymerase called polymerase-η (eta). Polymerase-η can replicate over the damage and is needed when cells enter S-phase in the presence of a DNA-replication. |
Symptoms
Some of the most common symptoms of XP include:
- A severe sunburn when exposed to only small amounts of sunlight. Often occurring during a child's first exposure to sunlight.
- Development of many freckles at an early age
- 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
- Spidery blood vessels
- Oozing raw skin surfaces
- Limited growth of hair on chest and legs
- Scaly skin
- Irregular dark spots on the skin
Treatment
The most obvious, and often important part of treatment, is avoiding exposure to sunlight. Keratoses can also be treated using cryotherapy or fluorouracil.[4] A few places specialize in XPS treatment, one of most notable being Camp Sundown in Craryville, New York.
Prognosis
Fewer than 40% of individuals with the disease survive beyond the age of 20. Some XP victims with less severe cases do manage to live well into their 40s.
In popular culture
These fictional characters have XP:
- Christopher Snow in Dean Koontz's Moonlight Bay Trilogy
- In the 2002 novel Going Out by Scarlett Thomas, Luke
- Children of the main character in Alejandro Amenábar's 2001 film, The Others
- In the Japanese movie Taiyou no Uta also known as Midnight Sun, the main character (Kaoru Amane)
- In the ITV series Ultraviolet, one of the humans is mistaken for a vampire because he avoids sunlight, when in fact he has XP.
- In the independent film Dark Side of the Sun (1988) with Brad Pitt as the main character suffering from XP.
- In the 2003 novel Second Glance by Jodi Picoult, Ethan Wakeman, the 9-year-old nephew of Ross Wakeman (the main protagonist)
- The 2003 Angela Johnson novel, A Cool Moonlight, centers on a girl who has XP and can never be in the sun. The family has gone to drastic measures to help make her life easier, and to make her feel like a normal 8-year-old.
- The 2011 film La permission de minuit by French director Delphine Gleize centers on a teenage boy with XP.
See also
References
- ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0721629210.
- ^ a b Li, Lei (January 8, 2007). "Chapter 3 Nucleotide Excision Repair". DNA REPAIR, GENETIC INSTABILITY, AND CANCER. World Scientific Publishing. pp. 75–76. ISBN 9812700145.
- ^ E. C. Friedberg, G. C. Walker, W. Siede, R. D. Wood, R. A. Schultz and T. Ellenberger (2006). DNA repair and mutagenesis. Washington: ASM Press. p. 1118. ISBN 978-1555813192.
{{cite book}}
: CS1 maint: multiple names: authors list (link) - ^ Template:Cite doi/10.1186.2F1757-1626-1-254
External links
- Information
- GeneReviews/NCBI/NIH/UW entry on Xeroderma pigmentosum
- An article about this disorder from DigiLander.iol.it (in English and Italian)
- DermNet systemic/xeroderma-pigmentosum
- Charities
- XP Society
- XP Family Support Group
- UK Patient Support Group
- An article about an untreated XP patient with no access to modernized medical care, with photos.
- Short films