Xeroderma pigmentosum
Encyclopedia
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
of DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
in which the ability to repair damage caused by ultraviolet
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
(UV) light is deficient. In extreme cases, all exposure to sunlight must be forbidden, no matter how small. Multiple basal cell carcinoma
Basal cell carcinoma
Basal-cell carcinoma is the most common type of skin cancer. It rarely metastasizes or kills. However, because it can cause significant destruction and disfigurement by invading surrounding tissues, it is still considered malignant. Statistically, approximately 3 out of 10 Caucasians may develop a...
s (basaliomas) and other skin malignancies frequently occur at a young age in those with XP. In fact, metastatic
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
malignant melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
and squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
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
Japanese people
The are an ethnic group originating in the Japanese archipelago and are the predominant ethnic group of Japan. Worldwide, approximately 130 million people are of Japanese descent; of these, approximately 127 million are residents of Japan. People of Japanese ancestry who live in other countries...
than in other groups.
The most common defect in xeroderma pigmentosum is an autosomal recessive genetic defect in which nucleotide excision repair
Nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA constantly requires repair due to damage that can occur to bases from a vast variety of sources including chemicals, radiation and other mutagens...
(NER) enzymes are mutated, leading to a reduction in or elimination of NER. If left unchecked, damage caused by ultraviolet (UV) light can cause mutations in individual cell's
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
DNA. If tumor suppressor genes (e.g. p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
) or proto oncogenes are affected, the result may be cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. Patients with XP are at a high risk for developing skin cancers, such as basal cell carcinoma
Basal cell carcinoma
Basal-cell carcinoma is the most common type of skin cancer. It rarely metastasizes or kills. However, because it can cause significant destruction and disfigurement by invading surrounding tissues, it is still considered malignant. Statistically, approximately 3 out of 10 Caucasians may develop a...
, for this reason.
Normally, damage to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
in epidermal cells occurs during exposure to UV light. The absorption of the high energy light leads to the formation of pyrimidine dimers
Pyrimidine dimers
Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions. Ultraviolet light induces the formation of covalent linkages by reactions localized on the C=C double bonds. In dsRNA, uracil dimers may also accumulate as a result of UV radiation...
, 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
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
then repairs the missing sequence, and ligase
DNA ligase
In molecular biology, DNA ligase is a specific type of enzyme, a ligase, that repairs single-stranded discontinuities in double stranded DNA molecules, in simple words strands that have double-strand break . Purified DNA ligase is used in gene cloning to join DNA molecules together...
"seals" the transaction. This process is known as nucleotide excision repair
Nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA constantly requires repair due to damage that can occur to bases from a vast variety of sources including chemicals, radiation and other mutagens...
.
Types
There are seven complementation groups, plus one variant form:| Type | Diseases Database Diseases Database The Diseases Database is a database that underlies a free website that provides information about the relationships between medical conditions, symptoms, and medications... |
OMIM | Gene | Locus Locus (genetics) In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map... |
Also known as/Description >- |Type A, I, XPA |
XPA XPA DNA repair protein complementing XP-A cells is a protein that in humans is encoded by the XPA gene.-Interactions:XPA has been shown to interact with ERCC1, Replication protein A1 and XAB2.-External Links:* -Further reading:... |
9q22.3 | Xeroderma pigmentosum group A - the classical form of XP >- |Type B, II, XPB |
XPB XPB XPB is an ATP dependent human DNA helicase that is a part of the TFIIH transcription factor complex.-Structure:The 3D structure of the archeael homologue of XPB has been solved by X-ray crystallography by Dr... |
2q21 | Xeroderma pigmentosum group B >- |Type C, III, XPC |
XPC XPC (gene) Xeroderma pigmentosum, complementation group C, also known as XPC, is a protein which in humans is encoded by the XPC gene. XPC is involved in the recognition of bulky DNA adducts in nucleotide excision repair.- Function :... |
3p25 | Xeroderma pigmentosum group C >- |Type D, IV, XPD |
XPD ERCC2 ERCC2, or XPD is a protein involved in transcription-coupled nucleotide excision repair.The XPD gene encodes for a 2.3-kb mRNA containing 22 exons and 21 introns. The XPD protein is a 760 amino acids polypeptide with a size of 87kDa... ERCC6 ERCC6 DNA excision repair protein ERCC-6 is a protein that in humans is encoded by the ERCC6 gene.-External links:*... |
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 |
DDB2 DDB2 DNA damage-binding protein 2 is a protein that in humans is encoded by the DDB2 gene.-Interactions:DDB2 has been shown to interact with CUL4A, CUL4B and DDB1.-External Links:* -Further reading:... |
11p12-p11 | Xeroderma pigmentosum group E >- |Type F, VI, XPF |
ERCC4 ERCC4 DNA repair endonuclease XPF is an enzyme that in humans is encoded by the ERCC4 gene.-Interactions:ERCC4 has been shown to interact with ERCC1 and FANCA.-External Links:* -Further reading:... |
16p13.3-p13.13 | Xeroderma pigmentosum group F >- |Type G, VII, XPG |
RAD2 ERCC5 ERCC5 DNA repair protein complementing XP-G cells is a protein that in humans is encoded by the ERCC5 gene.-External links:* -Further reading:... |
13q33 | Xeroderma pigmentosum group G and COFS syndrome type 3 >- |Type V, XPV |
POLH POLH Polymerase , eta, also known as POLH, is a protein which in humans is encoded by the POLH gene.-Function:This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases... |
6p21.1-p12 | Xeroderma pigmentosum variant - these patients suffer from mutation in a gene that codes for a specialized DNA polymerase DNA polymerase A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand.... called polymerase-η (eta) DNA polymerase eta DNA polymerase eta is a eukaryotic DNA polymerase involved in the DNA repair by translesion synthesis. The gene encoding DNA polymerase eta is POLH, also known as XPV, because loss of this gene results in the disease Xeroderma Pigmentosum Variant... . Polymerase-η can replicate over the damage and is needed when cells enter S-phase in the presence of a DNA-damage. |
Symptoms
Some of the most common symptomSymptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s of XP include:
- A severe sunburnSunburnA sunburn is a burn to living tissue, such as skin, which is produced by overexposure to ultraviolet radiation, commonly from the sun's rays. Usual mild symptoms in humans and other animals include red or reddish skin that is hot to the touch, general fatigue, and mild dizziness. An excess of UV...
when exposed to only small amounts of sunlight. Often occurring during a child's first exposure to sunlight. - Development of many freckleFreckleFor other uses of the word, see Freckles .Freckles are clusters of concentrated melanin which are most often visible on people with a fair complexion. A freckle is also called an "ephelis". Freckles do not have an increased number of melanin producing cells...
s 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
- BlisterBlisterA blister is a small pocket of fluid within the upper layers of the skin, typically caused by forceful rubbing , burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid called serum or plasma...
ing 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 cryotherapyCryotherapy
Cryotherapy is the local or general use of low temperatures in medical therapy or the removal of heat from a body part. The term "cryotherapy" comes from the Greek cryo meaning cold and the word therapy meaning cure...
or fluorouracil
Fluorouracil
Fluorouracil is a drug that is a pyrimidine analog which is used in the treatment of cancer. It is a suicide inhibitor and works through irreversible inhibition of thymidylate synthase. It belongs to the family of drugs called antimetabolites...
. 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 age 20 years. 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 KoontzDean KoontzDean Ray Koontz is a prolific American author best known for his novels which could be described broadly as suspense thrillers. He also frequently incorporates elements of horror, science fiction, mystery, and satire. A number of his books have appeared on the New York Times Bestseller List, with...
's Moonlight Bay TrilogyMoonlight Bay TrilogyThe Moonlight Bay Trilogy is a proposed trilogy of three novels by Dean Koontz. They revolve around the mysterious events in Moonlight Bay that are investigated by the main character Christopher Snow, who suffers from the genetic disorder Xeroderma pigmentosum.Only the first two books have been... - In the 2002 novel Going Out by Scarlett ThomasScarlett ThomasScarlett Thomas, born 1972 in Hammersmith, is an English author. She has written eight novels, including The End of Mr. Y and PopCo, and teaches Creative Writing at the University of Kent.-Biography:...
, Luke - Children of the main character in Alejandro AmenábarAlejandro AmenábarAlejandro Fernando Amenábar Cantos is a Spanish- Chilean film director. Amenábar was born in Santiago, Chile to a Spanish mother and Chilean father, but the family moved to Spain just one year after his birth...
's 2001 film, The OthersThe Others (2001 film)The Others is a 2001 psychological horror film by the Spanish-Chilean director Alejandro Amenábar, starring Nicole Kidman. It is inspired partly by the novella The Turn of the Screw.... - In the Japanese movie Taiyou no Uta also known as Midnight Sun, the main character (Kaoru Amane)
- In the ITVITVITV is the major commercial public service TV network in the United Kingdom. Launched in 1955 under the auspices of the Independent Television Authority to provide competition to the BBC, it is also the oldest commercial network in the UK...
series UltravioletUltraviolet (TV serial)Ultraviolet is a 1998 British television serial written and directed by Joe Ahearne and starring Jack Davenport, Susannah Harker, Idris Elba and Philip Quast. It was produced by World Productions for Channel 4.-Synopsis:...
, 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 PittBrad PittWilliam Bradley "Brad" Pitt is an American actor and film producer. Pitt has received two Academy Award nominations and four Golden Globe Award nominations, winning one...
as the main character suffering from XP. - In the 2003 novel Second GlanceSecond GlanceSecond Glance is a fiction novel written by American author Jodi Picoult.-Plot summary:Second Glance follows several characters throughout the book, in Jodi Picoult's typical fashion, flashing back and forth many decades to piece together the story. It is set in Comtosook, VT.The main plot is that...
by Jodi PicoultJodi PicoultJodi Lynn Picoult is an American author. She was awarded the New England Bookseller Award for fiction in 2003. Picoult currently has some 14 million copies of her books in print worldwide.-Early life and education:...
, Ethan Wakeman, the 9-year-old nephew of Ross Wakeman (the main protagonist) - The 2003 Angela JohnsonAngela Johnson (writer)Angela Johnson is an American children's book and poetry author with over 40 books to her credit since beginning her writing career in 1989. Her books for young children are simple yet poetic stories about African American families, friendships, and common childhood experiences such as moving...
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 GleizeDelphine GleizeDelphine Gleize is a French film director and screenwriter. She has directed ten films since 1998. Her film Carnages was screened in the Un Certain Regard section at the 2002 Cannes Film Festival.-Filmography:* Sale battars...
centers on a teenage boy with XP.
See also
- Biogerontology
- Cockayne syndromeCockayne syndromeCockayne syndrome is a rare autosomal recessive, congenital disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight , and premature aging...
- PhotophobiaPhotophobiaPhotophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...
- SenescenceSenescenceSenescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to those affecting the whole organism...
- List of cutaneous conditions
External links
Information- GeneReviews/NCBI/NIH/UW entry on Xeroderma pigmentosum
- An article about this disorder from DigiLander.iol.it (in English and Italian)
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