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BIO CHEMISTRY 2

Xeroderma pigmentosum:
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 endonucleasess. 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 OMIM Database

Gene

Locus

Also known as/Description

Type A, I, 29877 XPA

278700

XPA

9q22.3

Xeroderma pigmentosum group A - the classical form of XP

Type B, II, 29878 XPB

133510

XPB

2q21

Xeroderma pigmentosum group B

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Type C, III, 29879 XPC

278720

XPC

3p25

Xeroderma pigmentosum group C

Type D, IV, 29880 XPD

278730278800 XPDERCC6

19q13.2- Xeroderma pigmentosum group D or De Sanctis-Cacchione syndrome (can be q13.3, 10q11 considered a subtype of XPD)

Type E, V, 29881 XPE

278740

DDB2

11p12p11

Xeroderma pigmentosum group E

Type F, VI, 29882 XPF

278760

ERCC4

16p13.3Xeroderma pigmentosum group F p13.13

Type G, 29883 VII, XPG

278780133530 RAD2ERCC5 13q33

Xeroderma pigmentosum group G and COFS syndrome type 3

Type V, XPV

278750

POLH

6p21.1p12

Xeroderma pigmentosum variant - these patients suffer from mutation in a gene that codes for a specialized DNA polymerase called polymerase- (eta). Polymerase- 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

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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 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,

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.