Background

Xeroderma pigmentosum (XP) was first described in 1874 by Hebra and Kaposi. In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristic dry, pigmented skin. Xeroderma pigmentosum is a rare disorder transmitted in an autosomal recessive manner. It is characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development. 1 These manifestations are due to a cellular hypersensitivity to ultraviolet (UV) radiation resulting from a defect in DNA repair. The Medscape Pediatric Dermatology Resource Center and Skin Cancer Resource Center may be helpful.

Pathophysiology
The basic defect in xeroderma pigmentosum is in nucleotide excision repair (NER), leading to deficient repair of DNA damaged by UV radiation. This extensively studied process consists of the removal and the replacement of damaged DNA with new DNA. Two types of NER exist: global genome (GG-NER) and transcription coupled (TC-NER). The last decade has seen the cloning of the key elements of NER, and the process has been reconstituted in vitro. Seven xeroderma pigmentosum repair genes, XPA through XPG, have been identified. These genes play key roles in GG-NER and TC-NER. Both forms of NER include a damage-sensing phase, performed in GG-NER by the product of the XPC gene complexed to another factor. In addition, the XPA gene product has been reported to have an affinity for damaged DNA. Therefore, XPA likely also plays a role in the damage-sensing phase. Following detection of DNA damage, an open complex is formed. The XPG gene product is required for the open complex formation. The XPB and XPD gene products are part of a 9-subunit protein complex (TFIIH) that is also needed for the open complex formation. Subsequently, the damaged DNA is removed. The XPG and XPF genes encode endonucleases; however, the XPF gene product functions as an endonuclease when complexed to another protein. The resulting gap is filled in with new DNA by the action of polymerases. A xeroderma pigmentosum variant has also been described. The defect in this condition is not in NER, but is instead in postreplication repair. In the xeroderma pigmentosum variant, a mutation occurs in DNA polymerase . 2 Seven complementation groups, XPA through XPG, corresponding to defects in the corresponding gene products of XPA through XPG genes, have been described. These entities occur with different frequencies (eg, XPA is relatively common, whereas XPE is fairly rare), and they differ with respect to disease severity (eg, XPG is severe, whereas XPF is mild) and clinical features. Cockayne syndrome can rarely occur with XPB, XPD, and XPG.3 The continued presence of repair proteins at sites of DNA damage may also contribute to the pathogenesis of cutaneous cancer, as has been shown in XPD. 4

In addition to the defects in the repair genes, UV-B radiation also has immunosuppressive effects that may be involved in the pathogenesis of xeroderma pigmentosum. Although typical symptoms of immune deficiency, such as multiple infections, are not usually observed in patients with xeroderma pigmentosum, several immunologic abnormalities have been described in the skin of patients with xeroderma pigmentosum. Clinical studies of the skin of patients with xeroderma pigmentosum indicate prominent depletion of Langerhans cells induced by UV radiation. Various other defects in cell-mediated immunity have been reported in xeroderma pigmentosum. These defects include impaired cutaneous responses to recall antigens, decreased ratio of circulating T-helper cells to suppressor cells, impaired lymphocyte proliferative responses to mitogen, impaired production of interferon in lymphocytes, and reduced natural killer cell activity. In addition to their role in DNA repair, xeroderma pigmentosum proteins also have additional functions. For example, Frchet et al5 have shown that matrix metalloproteinase 1 is overexpressed in dermal fibroblasts from patients with XPC. They also demonstrated accumulation of reactive oxygen species in these fibroblasts in the absence of exposure to UV. They concluded that the XPC protein has roles in addition to NER. Matrix metalloproteinase 1 overexpression has been shown to occur in both aging of skin and carcinogenesis. XPG has been shown to form a stable complex with the transcription factor TFIIH, as mentioned above. Some manifestations of XPG/Cockayne syndrome in patients may therefore be due to abnormal transcription. 6 With respect to neurodegeneration seen in some cases of xeroderma pigmentosum, it may be associated with TC-NER rather than GG-NER. 7

Frequency
United States The frequency in the United States is approximately 1 case per 250,000 population. Group XPC is the most common form in the United States. International The frequency in Europe is approximately 1 case per 250,000 population. In Japan, it is higher, 1 case per 40,000 population. Groups XPA and XPC are the most common. Group XPA is the most common form in Japan.

Mortality/Morbidity
Individuals with this disease develop multiple cutaneous neoplasms at a young age. Two important causes of mortality are metastatic malignant melanoma and squamous cell carcinoma. Patients younger than 20 years have a 1000-fold increase in the incidence of nonmelanoma skin cancer and melanoma. The mean patient age of skin cancer is 8 years in patients with xeroderma pigmentosum, compared with 60 years in the healthy population. Actinic damage occurs between ages 1 and 2 years.

Race
Cases of xeroderma pigmentosum are reported in persons of all races.

Sex
An equal prevalence has been reported in males and females.

Age
The disease is usually detected at age 1-2 years.

CLINICAL
Section 3 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Acknowledgments Multimedia References

History
A history of severe persistent sunburn can be found in many patients. The history should focus on the relationship of the eruption to sun exposure, with a careful determination of its time course and morphology. As with most autosomal recessive disorders, usually no family history is present; the parents, being heterozygotes, are healthy. Additionally, a history of consanguinity may be elicited.

Physical
The disease typically passes through 3 stages. The skin is healthy at birth. Typically, the first stage appears after age 6 months. This stage is characterized by diffuse erythema, scaling, and frecklelike areas of increased pigmentation (see Media File

1). These findings, as would be expected from the pathophysiologic basis for the disease, are seen over light-exposed areas, appearing initially on the face. With progression of the disease, the skin changes appear on the lower legs, the neck, and even the trunk in extreme cases. While these features tend to diminish during the winter months with decreased sun exposure, as time passes, these findings become permanent. The second stage is characterized by poikiloderma. Poikiloderma consists of skin atrophy, telangiectasias, and mottled hyperpigmentation and hypopigmentation, giving rise to an appearance similar to that of chronic radiodermatitis (see Media File 2). Although telangiectasias also occur in the sun-exposed areas, they have been reported to arise in unexposed skin and even buccal mucosa. The third stage is heralded by the appearance of numerous malignancies, including squamous cell carcinomas, malignant melanoma, basal cell carcinoma, and fibrosarcoma. These malignancies may occur as early as age 4-5 years and are more prevalent in sun-exposed areas.

Photosensitivity should be suspected and evaluated in any patient with intermittent or persistent abnormalities on light-exposed areas. Photosensitivity in xeroderma pigmentosum is variable, but it generally occurs in the range of 290-320 nm. The minimal erythema dose is lower than normal at most wavelengths. o In xeroderma pigmentosum, the photosensitivity is acute in nature. The action spectrum for elicitation of the photosensitivity may be suggested by the seasonal or diurnal variability of the eruption and by any protective effect of window glass or sunscreens. Ocular problems8 occur in nearly 80% of individuals with xeroderma pigmentosum. The initial problems include photophobia and conjunctivitis. Eyelid solar lentigines occur during the first decade of life, and they might transform into malignant melanoma. o Ectropion, symblepharon with ulceration, repeated conjunctival inflammation, infections, and scarring might develop in these patients. In addition, vascular pterygia; fibrovascular pannus of the cornea; and epitheliomas of the lids, the conjunctivae, and the cornea can occur. o Finally, the propensity for malignancies, such as squamous cell carcinoma, basal cell carcinoma, sebaceous cell carcinoma, and fibrosarcoma, can also involve the eyes of patients with xeroderma pigmentosum. Neurologic problems8 are seen in nearly 20% of patients with xeroderma pigmentosum, more commonly in groups XPA and XPD. The severity of these problems is proportional to the sensitivity of xeroderma pigmentosum fibroblasts to UV radiation.
o o o o

The problems include microcephaly, spasticity, hyporeflexia or areflexia, ataxia, chorea, motor neuron signs or segmental demyelination, sensorineural deafness, supranuclear ophthalmoplegia,

and mental retardation. The neurologic problems might overshadow the cutaneous manifestations in some patients with xeroderma pigmentosum. De Sanctis-Cacchione syndrome refers to the combination of xeroderma pigmentosum and neurologic abnormalities (including mental retardation and cerebellar ataxia), hypogonadism, and dwarfism. The eMedicine Neurology article Xeroderma Pigmentosum may be of interest.

Causes
See Pathophysiology.

DIFFERENTIALS
Section 4 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Acknowledgments Multimedia References Acanthosis Nigricans Bloom Syndrome (Congenital Telangiectatic Erythema) Cockayne Syndrome Ephelides (Freckles) Hartnup Disease Hydroa Vacciniforme LEOPARD Syndrome Lupus Erythematosus, Acute Rothmund-Thomson Syndrome Werner Syndrome

Other Problems to be Considered

Basal cell nevus syndrome Porphyria

WORKUP
Section 5 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Acknowledgments Multimedia References

Lab Studies

No consistent routine laboratory abnormalities are present in xeroderma pigmentosum patients. The diagnosis of xeroderma pigmentosum can be established with studies performed in specialized laboratories. These studies include cellular hypersensitivity to UV radiation and chromosomal breakage studies, complementation studies, and gene sequencing to identify the specific gene complementation group. In the cellular hypersensitivity to UV radiation and chromosomal breakage studies, the xeroderma pigmentosum fibroblasts are stressed with different doses of UV radiation. Then, chromosomal breakage is evaluated in at least 100-200 cells, with at least 2 replicates for each dose. The cells from the patient are compared with those from the patient's parents (if possible, as they are obligate heterozygotes for xeroderma pigmentosum). Cells from unrelated healthy individuals are used as controls. To eliminate subjectivity, the person evaluating the chromosomal abnormalities is not informed as to which group the slides being examined belong. Prenatal diagnosis of xeroderma pigmentosum can be accomplished using similar chromosomal breakage studies on amniocytes from at-risk fetuses. o The xeroderma pigmentosum complementation groups can be determined using cell-fusion techniques followed by assessment of DNA repair or by gene sequencing. Prenatal diagnosis is possible by amniocentesis or chorionic villi sampling. Unscheduled DNA synthesis is the classic method for diagnosis. A modified technique using cultivation of both patient and control cells at the same time has also been described.9 A faster technique is the alkaline comet assay (single-cell gel electrophoresis assay). This method, in addition to being faster, requires fewer cells and does not require radioactivity. 10
o

Other Tests
Electroencephalographic findings may be abnormal.

Histologic Findings
The histologic findings of the first stage of the disease include hyperkeratosis and increased melanin pigment (this corresponds to the clinical freckling) in the basal cell layer (not necessarily accompanied by an increase in the numbers of melanocytes). Some rete ridges may be elongated, whereas other rete ridges may be atrophic. These findings may be accompanied by a chronic inflammatory infiltrate in the upper dermis. In the second stage, atrophy ensues, and the hyperkeratosis and the hyperpigmentation are more marked. Telangiectasia may be prominent. These findings correspond to poikiloderma. In addition, the epidermis may exhibit architectural disorder and atypia, and the dermis may be elastotic. Therefore, the histologic picture might be indistinguishable from that of actinic keratosis (see Media File 3). The histologic appearances of the various tumors that complicate xeroderma pigmentosum are seen in the third stage of xeroderma pigmentosum.

TREATMENT
Section 6 of 11 Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Acknowledgments Multimedia References

Medical Care
The goal of treatment is to protect the patient from sunlight. To this end, regular visits to the dermatologist might be necessary for the purposes of patient education and early detection and treatment of any malignancies.

The use of sunscreens in conjunction with other sun-avoidance methods (eg, protective clothing, hats, eyewear) can minimize UV-induced damage in

patients with xeroderma pigmentosum. Sunscreens should be applied to all exposed surfaces (including the hands, the back of the neck, the ears, the lower lips, and the anterior part of the chest) whenever UV exposure is expected. The 2 basic types of sunscreens are physical and chemical. Physical sunscreens scatter and reflect radiation. They contain large particles, such as titanium dioxide, zinc oxide, red ferric oxide, talc, and kaolin. Physical sunscreens block UV rays, infrared rays, and visible light. Their main disadvantage is that most are opaque, making them less cosmetically acceptable. New advances in physical sunscreens include microfine particles of titanium dioxide or zinc oxide, which are transparent. o Chemical sunscreens absorb UV radiation. Para-amino benzoic acid (PABA) was the first agent developed, but its potential to cause allergic reactions has limited its use. Some agents, such as benzophenones, mainly block UV-A, but they are weak UV-B photoprotectors. Avobenzone (Parsol 1789) has been introduced commercially in the United States. It is a much stronger UV-A photoprotector. Other agents, such as PABA esters, salicylates, and cinnamates, mainly block UV-B. Broad-spectrum chemical sunscreens include a combination of ingredients designed to block both UV-B and UV-A. Many of the new preparations are also designed to be water resistant. o No matter which sunscreen is used, the degree of protection is only partial. The effectiveness of sunscreens is expressed as a sun protection factor (SPF). The SPF is the ratio of the least amount of UV radiation required to produce a minimum erythema reaction with a sunscreen to the amount of the energy required to produce the same erythema without any sunscreen. Usually, sunscreens with a SPF of 15 or greater are recommended. o The eMedicine article Sunscreens and Photoprotection provides a detailed discussion of these agents. Oral retinoids have been shown to decrease the incidence of skin cancer in patients with xeroderma pigmentosum. 11 This therapy is limited by doserelated irreversible calcification of ligaments and tendons. Chemical therapy with 5-fluorouracil may be useful for actinic keratoses. Giannotti et al12 suggested in a case report that topical treatment with imiquimod and acitretin is an alternative to surgery. They prescribed imiquimod 5% cream to be applied 3 times weekly in combination with oral acitretin (20 mg/d) for 4-6 weeks. No adverse events were reported during treatment, and the tumors had resolved at the 6-month follow-up visit. A new approach to photoprotection is to repair DNA damage after UV exposure.13 This can be accomplished by delivery of a DNA repair enzyme into the skin by means of specially engineered liposomes. T4 endonuclease V has been shown to repair cyclobutane pyrimidine dimers resulting from DNA damage. Yarosh et al14 studied in a randomized fashion the effect of topically applied T4 endonuclease V in liposomes in xeroderma pigmentosum patients. Thirty patients were enrolled in this prospective double-blinded study. The annualized rate of new actinic keratoses was 8.2% among the patients assigned T4N5 liposome lotion and 25.9% among those assigned placebo. For basal cell carcinoma, the annualized rates of new lesions were
o

3.8% in the treatment group and 5.4% in the placebo group. No significant adverse effects were found among any of the patients. The topical application of DNA repair enzymes to the sun-damaged skin of patients with xeroderma pigmentosum lowered the rate of development of 2 forms of these lesions during 1 year of treatment. Gene therapy for xeroderma pigmentosum is still in a theoretical and experimental stage. Various methods of correcting the defects in xeroderma pigmentosum have been attempted in vitro and in animal studies using viral vectors (adenoviruses and retroviruses) carrying the gene replacement products. Ex vivo skin gene therapy, which refers to grafting skin that has the genetic defect corrected, may be useful in xeroderma pigmentosum in the future.15

Surgical Care
The malignancies associated with xeroderma pigmentosum should be completely excised.

Consultations
Consultation with an ophthalmologist is recommended because of the ocular problems associated with xeroderma pigmentosum. The use of UV-absorbing sunglasses should be included as part of the ocular management in patients with this disease. Artificial tears might be used. If corneal opacities supervene, corneal transplants can be performed. Consultation with a neurologist is also recommended because neurologic abnormalities are seen in 20% of patients with xeroderma pigmentosum.

Xeroderma Pigmentosum (XP)

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder, where there is an impairment of the skin's ability to repair damage from ultraviolet light. Affected individuals appear to age more rapidly and develop dryness of the skin. More importantly, they have a vastly increased tendency to develop skin tumours and eye damage from ultraviolet (UV) light.

Epidemiology

Xeroderma pigmentosum (XP) is very rare but appears to be present throughout the world and in every ethnic group. There are currently approximately 100 diagnosed cases in the UK. The international incidence is around 1 in 250,000. Some areas such as Japan and the Middle East have higher rates of XP.2

Types of XP

Seven forms have been described, denoted by letters (XPA - XPG). There is an 8th type known as XP variant (XPV). Each has a different genetic characteristic. XP variant was formerly known as pigmented xerodermoid.

DeSanctis-Cacchione syndrome

In the past, XP with any neurological abnormality was classified as DeSanctis-Cacchione syndrome. Currently, this syndrome refers to XP with severe neurological disease. The complete syndrome is very rare, but individuals with XP may have one or more of its neurological features (see below).

Presentation

1,2

The main features of XP are photosensitivity and a high incidence of skin cancer at very young age. Presenting features are:

Skin features
Sunburn occurs after minimal sun exposure, often noticed in infancy. Skin changes - which occur in 3 stages:
1. 2. Dry or scaly skin, freckling and irregular areas of hyperpigmentation. Poikiloderma (comprising irregular patches of hyper- and hypo-pigmentation, telangiectasia and atrophy).

3.

These changes are seen first over the areas most exposed to light, initially on the face. Later, lesions may develop on unexposed skin.

Skin cancers and develop early; the median age is 8 years (though this is prevented by good protection - see treatment and prognosis sections). These are: solar keratoses (premalignant), squamous cell carcinoma, basal cell carcinoma and malignant melanoma. They may occur as early as age 4 or 5 years old and are more prevalent in areas exposed to sun. The anterior tongue is also vulnerable.

Eye features

Eye features occur in the anterior, exposed part of the eye:

Photophobia. Conjunctival inflammation and keratitis. Tumours of conjunctiva and eyelids - benign or malignant. Atrophy of eyelids leading to ectropion or entropion.

Neurological features
Neurological problems occur in 20% of XP sufferers.4 They can be mild or severe. Possible features are: hypo-reflexia, sensorineural deafness, spasticity, poor co-ordination, seizures,
acquired microcephaly or progressive intellectual impairment.

These seem to be unrelated to UV exposure, but tend to occur in those whose skin is most severely
affected by UV.

The DeSanctis-Cacchione syndrome is XP with severe neurological involvement, including dwarfism

and delayed sexual development.

Differential diagnosis
There are other causes of photosensitivity, e.g congenital erythropoietic porphyria.1 There are several other genetic conditions with photosensitivity due to defective DNA repair.2

Investigations and diagnosis

be referred to a dermatologist.

Early diagnosis is important to prevent complications. Babies and children with photosensitivity should Marked freckling of sun-exposed areas under age 2 years is unusual in normal children and should
raise the suspicion of XP.

Skin cancer in children is rare and merits investigation for an underlying cause. The diagnosis is made by skin biopsy with fibroblast culture. The fibroblasts can be tested for DNA
repair, UV sensitivity and unscheduled DNA synthesis.

Genetic testing is available for XPA and XPC types. Prenatal diagnosis is usually possible.

Management
Currently, there is no specific treatment for XP. Management involves preventing damage and dealing with damaged tissues at an early stage.

Avoidance of UV light

1,5,6

Total protection from UV light greatly improves the prognosis and reduces skin changes and cancers. This is achieved by:

Restrict outdoor activities to night time. If outdoors during the day, cover the skin completely. Clothing: long opaque clothes, sunhats, UV protective sunglasses with side shields, long hairstyles;
custom made face shields are also available.

Protective film on windows (normal glass filters some but not all UV light). Some indoor lighting emits UV: light sources may need to be changed or protected. Standard
incandescent light bulbs do not emit UV.

Frequent application of high-factor sunscreen, even indoors.

Surveillance

1,2

Dermatologist reviews 3-monthly for skin cancer surveillance. Relatives can be taught to do skin checks between appointments. Ophthalmology examinations annually. Early surgical removal of skin lesions. Regular neurological review and hearing tests.

Drug treatments

Vitamin D supplements may be needed, since sunlight (a major source of vitamin D) is excluded.1,2 Moisturisers: skin emollients and artificial tear preparations (soft contact lenses may also protect against
dry eyes).2

Oral retinoids can reduce the incidence of skin cancer, but side-effects limit their use.2,7 A possible development is T4N5 lotion. This contains a bacterial enzyme, T4 endouclease. which
repairs some DNA defects. In one small trial, it reduced the development of solar keratoses in XP patients. However, it is not yet licensed.8

Treatment of neoplasms

Premalignant lesions, e.g. actinic keratoses: topical 5-fluorouracil or cryotherapy. Larger areas can be
treated by dermabrasion or dermatome shaving.

Skin and eye tumours are treated in the same way as for those without XP, but with caution to conserve
undamaged skin (because of the likely need for further procedures).

Large areas with skin tumours can be grafted using unexposed skin.

Other treatments

Genetic counselling if parents are considering further pregnancies. Prenatal diagnosis may be possible. Support and counselling for patients and families, because of the severe lifestyle restrictions involved. Avoid tobacco. Siblings should be protected from UV until XP can be excluded.

Complications

2,4

Skin and eye tumours, as above. The risk of these is approximately a thousand times normal. Vitamin D deficiency (and its complications) have been reported. Some patients with XP are hypersensitive to X-rays, so a small test dose is advised before therapeutic
X-radiation.9

There may be increased tobacco sensitivity. Lung cancer at a relatively young age has been reported in
XP patients who smoke.

 Other cancers: there seems to be an increased risk of buccal cancer (probably due to UV in the oral
cavity). There may be a higher rate of internal cancers, perhaps due to the same DNA repair defect in combination with other toxins.

Prognosis
The prognosis varies with the severity of the genetic disorder, the success in avoiding UV light and vigilance of screening. It also depends on neurological involvement.10,4 Previously, the prognosis was a reduced life expectancy due to skin cancers or neurological complications. However, more recent information suggests that a normal lifespan is possible for patients without neurological problems who are fully protected from UV.1,6

History
XP was first described in 1870 by Hebra and Kaposi. The disease has a unique place in medical history: when Cleaver identified the basis of xeroderma pigmentosum in 1969,11 it provided the first clear understanding of the central role played by DNA mutation in cancer.

www.emedicine.com/derm/TOPIC462.HTM Sebenarnya, postingan ini didorong oleh pertanyaan seseorang dalam Yahoo! Answer (Y!A). Inilah link pertanyaan dan jawabannya. Saya biasa menggunakan nama adhikhresna dalam dunia maya ini. Menurut Erlich (1989) PCR adalah suatu metode in vitro yang digunakan untuk mensintesis sekuens tertentu DNA dengan menggunakan dua primer oligonukleotida yang menghibridisasi pita yang berlawanan dan mengapit dua target DNA. Kesederhanaan dan tingginya tingkat kesuksesan amplifikasi sekuens DNA yang diperoleh menyebabkan teknik ini semakin luas penggunaannya (Saiki et al., 1988 dalam Wahyudi, 2001). Pada dasarnya reaksi PCR adalah tiruan dari proses replikasi DNA in vivo, yaitu dengan adanya pembukaan rantai DNA (denaturasi) utas ganda, penempelan primer (annealing) dan perpanjangan rantai DNA baru (extension) oleh DNA polimerase dari arah terminal 5 ke 3. Hanya saja pada teknik PCR tidak menggunakan enzim ligase dan primer RNA. Secara singkat, teknik PCR dilakukan dengan cara mencampurkan sampel DNA dengan primer oligonukleotida, deoksiribonukleotida trifosfat (dNTP), enzim termostabil Taq DNA polimerase dalam larutan DNA yang sesuai, kemudian menaikkan dan menurunkan suhu campuran secara berulang beberapa puluh siklus sampai diperoleh jumlah sekuens DNA yang diinginkan. Proses PCR memerlukan sejumlah siklus untuk mengamplifikasi suatu sekuens DNA spesifik. Setiap siklus terdiri atas tiga tahap, yaitu denaturasi, annealing (hibridisasi), dan ekstensi (polimerasi). Denaturasi dilakukan pada suhu 90-95C, sehingga terjadi pemisahan utas ganda DNA menjadi dua utas tunggal DNA yang menjadi cetakan (template) tempat penempelan primer dan tempat kerja DNA polimerase. Selanjutnya, suhu diturunkan untuk penempelan primer oligonukleotida pada sekuens yang komplementer pada molekul DNA cetakan. Tahap ini disebut annealing. Suhu campuran diturunkan sampai mencapai ~55C atau sesuai melting temperature (Tm) dari primer oligonukleotida (Glick & Pasternak, 2003).

Selama tahap ini, primer berpasangan dengan sekuens komplementernya di dalam DNA cetakan. Primer oligonukleotida melekat pada masing-masing utas tunggal DNA dengan arah yang berlawanan; satu primer melekat pada ujung utas DNA sense, sedangkan primer yang lain melekat pada ujung utas DNA antisense. Tahap selanjutnya adalah tahap ekstensi yang dilakukan pada suhu 72C. Suhu ini merupakan suhu optimum untuk kerja enzim Taq DNA polimerase. Pada tahap ini enzim Taq DNA polimerase mengkatalis reaksi penambahan mononukleotida pada primer yang sesuai dengan utas DNA komplemen yang berada di sebelahnya. Suhu pada setiap tahap diatur sedemikian rupa sehingga dihasilkan amplifikasi sekuens target DNA yang efisien (Saiki et al., 1989 dalam Wahyudi, 2001). Tahapan kerja PCR secara singkat digambarkan dalam Gambar. Saya sudah upload gambar, silahkan klik link berikut ini untuk mendapatkannya (di sini). Keterangan untuk Gambar tersebut: 1. Tahap denaturasi; 2. Tahap annealing; 3. Tahap ekstensi; 4. Perkembangan pada siklus selanjutnya; P: Polimerase. Saya sengaja memposting gambar di luar, karena keterbatasan space naksara. Semoga nantinya ada dana untuk mengupgrade spacenya (saat ini Cuma 100MB). Ada juga Degenerate PCR. Degenerate PCR mempunyai banyak kesamaan dengan PCR biasa. Perbedaan utamanya adalah primer spesifik pada PCR biasa diganti dengan primer mix. Banyak gen dalam satu famili mempunyai struktur yang mirip. Dengan menderetkan sekuens nukleotida dari sejumlah nukleotida yang berhubungan akan dapat ditemukan bagian nukleotida yang konserf (conserve). Berdasarkan informasi tersebut dapat ditemukan motif nukleotida yang konserf yang dapat digunakan sebagai titik awal pembuatan primer degenerate PCR (Koelle, 1996). http://naksara.net/Aquaculture/Genetic/apakah-itu-pcr-polimerase-chain-reaction-danbagaimana-cara-kerjanya.html

An inherited skin disorder characterized by photosensitivity with severe sunburn in infancy, the development of numerous pigmented spots resembling freckles, larger atrophic lesions associated with telangiectasis, and multiple solar keratoses. Transmitted in an autosomal recessive manner, xeroderma pigmentosa involves a defect in nucleotide excision repair (NER), leading to deficient repair of DNA damaged by UV radiation and chromosome breakage. Individuals with this disease develop multiple malignant cutaneous neoplasms at an early age and may suffer from severe ophthalmic and neurologic abnormalities. --2004 - (Source - Diseases Database) A rare genetic condition characterized by an eruption of exposed skin occurring in childhood and photosensitivity with severe sunburn; inherited as a recessive autosomal trait in which DNA repair processesm are defective so they are more likely to chromosome breaks and cancers when exposed to ultraviolet light - (Source - WordNet 2.1)

Xeroderma pigmentosum is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that Xeroderma pigmentosum, or a subtype of Xeroderma pigmentosum, affects less than 200,000 people in the US population. Source - National Institutes of Health (NIH) Ophanet, a consortium of European partners, currently defines a condition rare when it affects 1 person per 2,000. They list Xeroderma pigmentosum as a "rare disease".

http://www.wrongdiagnosis.com/x/xeroderma_pigmentosum/intro.htm http://eprints.ums.ac.id/521/1/infokes_8_(1)_arina_maliya.pdf(pdf)