Genetic determinants of learning disability Flashcards
1
Q
Define learning disability
A
- Significantly reduced ability to understand new or complex information
- Reduced ability to cope independently which starts before adulthood with lasting effects on development
2
Q
Define autisic spectrum disorders
A
- Developmental conditions present from birth
- Characterised by impaired social interaction, impaired social communication and impaired imagination
3
Q
What is the cause?
A
- Genetics
- Problems during pregnancy and birth - infections, teratogens, prematurity
- Incidents after birth - serious illness, head injury, poor nutriotion, exposure to toxins
4
Q
Cytogenetic vs molecular genetic abnormalities
A
- Cytogentic = can be seen under microscope
- Molecular = cannot be seen under microscope
5
Q
What are the main causes of cytogenetic abnormality?
A
- Aneuploidy - abnormalities in chr number
- Translocations = robertsonian, reciprocal
- Deletions/ duplications
6
Q
What is a Robertsonian translocation?
A
- Only occurs on 13, 14, 15, 21, 22
- Get 2 acrocentric chromosomes stuck end to end
- Carrier has 45 chromosomes, but normal amount of genetic material
- Affected has 46 chromosomes, but extra copy of one (usually 21)
7
Q
What is a reciprocal translocation?
A
- Involve any part of any chromosome
- Exchange of material between the 2 chromosomes
- Carrier completely normal
- Can result in offspring with unbalaced amounts of the 2 chromosomes
8
Q
What is 4p-(wolf-Hirschhorn)?
A
- 4p-9a large chunk of Chr4 is deleted - malformation of kidney, cardiac disease, differential features
- Can see the differences under microscope
9
Q
What is caused by a 22q11 microdeletion?
A
- Significant speech and language difficulties
- Cleft palate
- Congenital heart disease
- Hypocalcaemia
- Mild to moderate learning difficulties
- Renal abnormalities
- AKA DiGeorge syndrome
10
Q
What is FISH?
A
- Fluorescent in situ hybridisation
- Uses fluorescent probe complimentary to specific part of the genome you want to look at - if present, it will fluoresce
- can be used when looking for deletions (eg 2 copies of each bit of DNA should be present, will see by 2 separate lights)
11
Q
What is arrayCGH?
A
- An untargeted test, dont need to know what you are looking for
- Uses probes all along the Chromosome, will pick up any microsatellites
- Array is done to make it less likely to fail, allowing them to hybridise on the slide anywhere, then a computer will arrange it correctly
- Yellow is normal; red = duplication; green = deletion
12
Q
What symptoms does a 7q11.2 deletion cause?
A
- William’s syndrome
- FISH shows that the elastin gene isnt present on both alleles - deletion
- Learning difficulties and speech delay
13
Q
What symptoms does a 15q11.2 deletion cause?
A
- often inherited from parent with few problems
- variable phenotype
- no reliably recognisably dysmorphology
- seizures
- mild-moderate delay
14
Q
How do we look for single gene disorders?
A
- Sanger sequencing if we know what we are looking for
15
Q
What is phenylketonuria?
A
- have no/ a defect in phenylalanine hydroxylase
- Means that they are unable to turn phenylalanine into tyrosine, causing its accumulation
- Developmental delay
- Beahvioural/ social probs
- seizures
- hyperactivity
- Growth retardation
- Eczema
- Microcephaly
- A musty odour of child
