| Xeroderma pigmentosum | |
|---|---|
| Classification and external resources | |
| ICD-10 | Q82.1 |
| ICD-9 | 757.33 |
| DiseasesDB | 14198 |
| eMedicine | derm/462 neuro/399 |
| MeSH | D014983 |
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.
Contents |
There are seven complementation groups, plus one variant form:
| Type | Diseases Database | OMIM | Gene | Locus | Also known as/Description |
| Type A, I, XPA | 29877 | 278700 | XPA | 9q22.3 | Xeroderma pigmentosum group A - the classical form of XP |
| Type B, II, XPB | 29878 | 133510 | XPB | 2q21 | Xeroderma pigmentosum group B |
| Type C, III, XPC | 29879 | 278720 | XPC | 3p25 | Xeroderma pigmentosum group C |
| Type D, IV, XPD | 29880 | 278730 278800 | 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 | 29881 | 278740 | DDB2 | 11p12-p11 | Xeroderma pigmentosum group E |
| Type F, VI, XPF | 29882 | 278760 | ERCC4 | 16p13.3-p13.13 | Xeroderma pigmentosum group F |
| Type G, VII, XPG | 29883 | 278780 133530 | RAD2 ERCC5 | 13q33 | Xeroderma pigmentosum group G and COFS syndrome type 3 |
| Type V, XPV | 278750 | 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-damage. |
Some of the most common symptoms of XP include:
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.
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.
These fictional characters have XP:
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