Genetic Disease

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Genetic Disease

• By Jean Liu
• ID 08301016041

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General Facts

• Caused by an abnormality in an individuals
  genome
• Can also be caused by environmental factors
• The abnormality can range from minuscule to major
• Point mutation (P) insertion/deletion entirely
  inside one gene
• Deletion (D) removal of a gene or genes
• C whole chromosome extra, missing or both
• Trinucleotide repeat disorder (T) gene is
  extended in length

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Xeroderma PigmentosumWhat Is It ?

• Very rare inherited skin disorder
• A person is highly sensitive to the sunlight
  (photosensitive)
• Autosomal recessive genetic disorder
• DNA repair ability of repair damage caused by
  ultraviolet (UV) light
• Six times more common in Japanese people than in
  other groups
• Around 1 in 40,000
• Equal numbers of male and female patients
• Less than 40 of individuals with XP survive
  beyond age 20 years
• Those with milder disease may survive beyond
  middle age

Malignancy medical condition that can
progress,
potentially result in death eg tumors
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Xeroderma PigmentosumTypes
Type Gene Locus
Type A, I, XPA XPA 9q22.3 Absent or minimal DNA repair activity
Type B, II, XPB XPB 2q21 Few patients
Type C, III, XPC XPC 3q25 Most common, 1/3 of all patients
Type D, IV, XPD XPD ERCC6 19q13.2-q13.3, 10q11 Second most common
Type E, V, XPE DDB2 11p12-p11
Type F, VI, XPF ERCC4 16p13.3-p13.13
Type G, VII, XPG RAD2 ERCC5 13q33
Dominant Type
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Xeroderma PigmentosumHow is it inherited ?

• Genetic Condition
• Can be passed from generation to generation in
• Autosomal recessive inheritance patter
• Mutation must be present in both copies of the
  gene
• Carrier one copy of the gene mutation
• When both parents are carrier, there is a 25
  chance that the child will be affected

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Xeroderma PigmentosumSymptoms

• Skin
• Eyes
• Neurological

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Xeroderma PigmentosumSkin Symptoms

• Severe sunburn after a short sun exposure
• May last for several weeks
• Usually happens during a childs first exposure
  to the sun
• Development of freckles at an early age
• Irregular dark spots
• Thin skin
• Excessive dryness of the skin
• Premature aging of skin, lips, eyes, mouth and
  tongue
• More than 1,000 times the risk of developing skin
  cancer

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Xeroderma PigmentosumEye Symptoms

• Occur nearly 80 of the patients
• Eyes are very sensitive to the sun (photophobia)
• Irritated
• Bloodshot
• Cloudiness of the cornea
• Darkening of the skin of the eyelids

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Xeroderma PigmentosumNeurological Symptoms

• Only occur in 20-30 of people with XP
• Tend to get worse over time
• Hearing loss
• Microcephaly
• Spastic muscles
• Stiffness or tightness of
• the muscles
• Seizures
• Intellectual impairment
• Poor coordination

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Xeroderma PigmentosumClassifications

• Mild
• Light brown freckles on face
• Moderate
• Dark brown freckles on face
• Burning on exposed parts of the body
• Photophobia
• Severe
• Serious dark brown freckles
• Burning on exposed/unexposed parts of the body
• Cutaneous changes
• Ocular changes

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Xeroderma PigmentosumCause
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Xeroderma PigmentosumComplications

• Skin tumors
• Most patients die of skin cancer early in
  adulthood
• Eye tumors
• Vitamin D deficiency
• Some are hypersensitive to X-rays
• Patients who smoke may develop lung cancer at a
  relatively young age

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Xeroderma PigmentosumDiagnosis

• Tests
• Blood samples
• Urine samples
• Skin biopsy
• Eye exam
• Clouding of the cornea loss of transparency of
  the cornea
• Keratitis front part of the eye becomes
  inflamed
• Lid tumors
• Blepharitis inflammation of the eyelash
  follicles
• Fibroblast culture
• DNA repair
• UV sensitivity
• Aminocentesis
• Test before the birth of the child - take sample
  of fluid from the sac around the baby

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Xeroderma PigmentosumTreatment

• There is no cure for XP so far
• Many management methods to cope with the problems

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Xeroderma PigmentosumManagement

• Physically
• Reducing exposure to the sun
• Sun glasses
• Clothing (long sleeves, long pants, gloves)
• Optical filtration
• Lots and lots of sunscreens
• Chemically
• Reducing the number of keratoses with
  Isotretinoin
• Housing
• Halogen lamps

Keratoses keratin (on the skin)
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Xeroderma PigmentosumManagement

• Two parts
• Headgear
• Protect head and face
• Suit
• Covering the rest of the body
• Filtering 100 UV-light

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Xeroderma PigmentosumPrevention

• Focuses more on future problems
• Frequent check-ups and examinations
• Skin specialist (dermatologist)
• Eye specialist (ophthalmologist)

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Xeroderma PigmentosumA Case In China

• Wan Lao Yang the girl who lives in the dark
• An XP patient
• Her facial tumors made it impossible for her to
  wear the UV protective suit
• The cancer had spread to her lungs
• Died on June 2006

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Genetic Disease

• By Jean Liu
• ID 08301016041