PowerPoint Presentation - What Causes XP?

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Xeroderma Pigmentosum Nov 21st 2005
Diana Mok Kaitlin Myers Thao Nguyen T. Nguyen
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Introduction

• First described in 1874 by Hebra and Kaposi
• 1882 the term XP is first used
• Rare disorder transmitted in an autosomal
  recessive manner
• Characterized by photosensitivity, pigmentary
  changes, premature skin aging, and malignant
  tumor development.

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• Incidence the US 1 in 250,000 (XPC most
  common)
• Europe 1 in 250,000 (XPC
  most common)
• Japan 1 in 40,000 (XPA
  most common)
• Cases reported in all races
• Sex equal incidence
• Age Usually detected at 1 or 2 years

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Symptoms

• Unusually severe sunburn after a short sun
  exposure
• Freckles at early age
• Continued sun exposure leads to changes
  irregular dark spots, thin skin, excessive
  dryness, rough-surfaced growths, skin cancer

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• Normally begins during infancy and almost always
  before 20 years of age
• Eyes sensitive to the sun, easily irritated,
  bloodshot and clouded noncanerous or cancerous
  growths on the eyes may occur
• Skin cancer first skin cancer may develop before
  the person is 10, many other skin cancers may
  continue to form often on the face and
  sun-exposed parts of the body.

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• 20 XP patients may suffer from nerve-related
  problems deafness, poor coordination, spastic
  muscles, or developmental delay
• Some may be very short and may not develop normal
  sexual characteristics
• Neurological problems worsen over time if present

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Diagnosis

• Measuring the DNA repair factor from skin or
  blood samples
• Cellular hypersensitivity to UV radiation and
  chromosomal breakage studies
• Complementation studies
• Gene sequencing
• Antenatal diagnosis amniocentesis, chorionic
  villi sampling

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What Causes XP?

• Defect in nucleotide excision repair (NER)
• 2 types of NER
• Global Genome (GG-NER)
• Transcription coupled (TC-NER)
• Defected, unable to repair DNA damaged by UV
  radiation

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Where Does XP Occur?

• 7 repair genes
• XPA-9q22.3
• XPB-2q21
• XPC-3p25
• XPD-19q13.2-q13.3
• XPE-11p12-p11
• XPF-16p13.3-p13.2
• XPG-13q33
• All play key roles in GG-NER TC-NER

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Normal DNA Repair Process

• When DNA is damaged, both NERs have a damage
  sensing phase.
• Detection in GG-NER is done by the product of the
  XPC gene.
• XPA gene product can also detect DNA damage.

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• After detection, open complex formed.
• XPG gene required.
• Products of XPB XPD part of 9-subunit protein
  complex (TFIIH) needed for complex formation as
  well.
• Damaged DNA removed.

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• XPG XPF gene encode endonucleases.
• XPF gene product also functions as an
  endonuclease.
• Gap filled with new DNA by action polymerase.

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How Bad is It?

• Replication error not in NER but after the post
  replication repair.
• XPA-XPG corresponds to defects in gene process.
• XPA-common
• XPE-rare
• Disease Severity
• XPF-mild
• XPG-severe

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• UV-B radiation causes immunosuppressive effects
  that may be pathogenesis of XP.
• XP patients skin have depletion of Langerhans
  cells due to UV radiation.
• Defects in cell-mediated immunity reported in XP
• impaired response to recall
  antigens
• decreased circulatory T-helper
  cells to supressor cells ratio
• reduced natural killer cell
  activity

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Treatments

• Sunscreens and other sun avoidance methods
  (protective clothing, hats, eyewear)
• Oral retinoids gt dose-related irreversible
  calcification of ligaments and tendons
• Chemical therapy

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• Repair DNA damage after UV exposure by delivery
  of a DNA repair enzyme into the skin by means of
  specially engineered liposomes (under studies)
• Complete excision of malignancies
• Ophthalmologic and neurologic consultations
  recommended

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Personal Account

• Fatima
• Originally from the Dominican Republic
• Diagnosed with light-sensitivity as child
• Doctors/family unsure how to treat her
• Forty radiation treatments
• Now an active member of the XP society

Im very grateful to God that Im still alive.
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• Polly
• Never liked the outdoors as a child
• Fell ill in sunlight
• Parents signed her up for several outdoor sports
  to shake her out of it
• As adult found the XP website, sent in a letter
• Now learning how to protect herself, balance her
  time, and enjoy her life.

I cant find any doctor in this area (West
Virginia) who has any concept of what it means
to have a light sensitivity disorder.
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• Shelley
• Shelley is ten years old
• Member of the group Children of the Moon
• Has created her own website
• Has house and car with UV-protected windows
• Goes to school with UV protected windows
• Likes the Backstreet Boys, her dog, and Nintendo

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The XP Society and Camp Sundown

• Devoted to education awareness, information
  exchange, and promoting medical research
• Camp Sundown is for all ages, and provides a
  place for those affected to form relationships
  with others with XP

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Works Cited

• http//xps.org
• www.moonchildren.com
• http//www.emedicine.com/DERM/topic462.htm
• http//www.cc.nih.gov/ccc/patient.education/pepubs
  /xeroderma.pdf
• http//hometown.aol.com/pelony7/images/small20of
  20sun20in20moon.jpg
• http//www.skipressworld.com/images/daily_2005/04/
  ski20press20-20sunscreen203.jpg
• http//phobos.ramapo.edu/pbagga/xp.JPG
• http//www.zdf.de/ZDFde/img/106/0,1886,2396522,00.
  jpg
• http//www.zdf.de/ZDFde/img/106/0,1886,2396522,00.
  jpg
• http//www.reactome.org/cgi-bin/eventbrowser?DBgk
  _currentFOCUS_SPECIESHomo20sapiensID17134