Transcript Genetic Disease

Genetic Disease
By: Jean Liu
ID: 08301016041
General Facts
Caused by an abnormality in an individual’s 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
Xeroderma Pigmentosum
What 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
Xeroderma Pigmentosum
Types
Type
Gene
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
Locus
Xeroderma Pigmentosum
How 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
Xeroderma Pigmentosum
Symptoms
Skin
Eyes
Neurological
Xeroderma Pigmentosum
Skin Symptoms
Severe sunburn after a short sun exposure
May last for several weeks
Usually happens during a child’s 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
Xeroderma Pigmentosum
Eye 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
Xeroderma Pigmentosum
Neurological 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
Xeroderma Pigmentosum
Classifications
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
Xeroderma Pigmentosum
Cause
Nucleotide excision repair (NER) enzymes are mutated
NER - DNA repair mechanism
Reduction or elimination of NER
Unrepaired damage can lead to mutations, changing the information of the DNA in
the individual
If mutation affect the important genes, this can lead to serious disease
For example: p53, tumor suppressor genes, this order can lead to cancer
Xeroderma Pigmentosum
Complications
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
Xeroderma Pigmentosum
Diagnosis
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
Xeroderma Pigmentosum
Treatment
There is no cure for XP so far
Many management methods to cope with the
problems
Xeroderma Pigmentosum
Management
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)
Xeroderma Pigmentosum
Management
Two parts
Headgear
Protect head and face
Suit
Covering the rest of the
body
Filtering 100% UV-light
Xeroderma Pigmentosum
Prevention
Focuses more on future problems
Frequent check-ups and examinations
Skin specialist (dermatologist)
Eye specialist (ophthalmologist)
Xeroderma Pigmentosum
A 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
Genetic Disease
By: Jean Liu
ID: 08301016041