L21 Genetic Testing 2 Flashcards
Testing late in pregnancy
see onenote
Testing after birth - Guthrie spots
see onenote
- PKU, CF, hypothyroidism
- first condition screened was for PKU
- in Victoria, screens for 25 conditions
Neonatal screening
see onenote
Guthrie cards
see onenote
The neonatal heel prick is a blood collection procedure done on newborns. It consists of making a pinprick puncture in one heel of the newborn to collect their blood
PKU
Phenylketonuria
- 1:12,000 in newborns
- phenylalanine hydroxylase gene PAH gene
- chromosome 1
- autosomal recessive
- variable expression depending on mutation and quantity of enzyme
Metabolism of phenylalanine
see onenote
Accumulation of phenylalanine - causes permanent brain damage, needs to pick up PKU very quickly, very treatable
- Usually have a musty smell due to the phenylalanine
PKU - treatment
- diet low in phenylalanine and supplemented with tyrosine
- controversy how long diet is maintained
- diet resumed prior to and during pregnancy
Screening neonates for Cystic fibrosis
- neonatal testing using blood spot collected in first week
- initial screen: elevated immunoreactive trypsin levels
- recall 1% with elevated IRT
Collect blood spots, similar to PKU
- Screen for IRT, indicator that they may have cystic fibrosis (CF)
- Found over 2000 CF mutations, for what mutations do we screen for? Very expensive to screen for all 2000 mutations
- Babies with elevated IRF get called in
Newborn screening - CF (correlates to two slides)
see onenote slides
Screening for about 12 mutations but have now increased it to 21 mutations
- If they screen the blood and found 2 mutations => will probably have CF
- 1 mutation => sweat test
- CF is a transporter mutation, Cl- transporter is disrupted => very salty sweat
- Make baby sweat and measuring Cl- concentration
F508del mutation is the most common CFTR mutation in the world
CFTR = cystic fibrosis transmembrane conductance regulator
CFTR mutation types
see onenote
currently 2019 mutations listed in CFTR mutation database
Cystic fibrosis - F508del
see onenote
PCR region of exon 10 with p.F508 del mutation to detect deletion on gel
Sweat test
see onenote
- testing for Cl- concentration
Victorian study: 1998 - 2008
see onenote
Childhood testing - paternity testing
No laws in Australia that prevents genetic testing of children
HGSA
- oversees cytogenetic labs
- makes recommendations for clinicians to follow
- recommends that consent from both parents should be obtained in paternity testing of children
Paternity testing
- Some labs promote paternity testing
- 2 levels:
1. Accredited and can be used in court
2. Aren’t accredited, test can’t be used in court - NATA accredited
Childhood testing - late onset diseases
see onenote slides
should children be tested?
- conditions for which there is potential medical benefit in the immediate future, pre-symptomatic and predictive testing should be offered
- conditions for which there is no potential medical benefit in the immediate future, pre-symptomatic and predictive testing should not be undertaken
Carrier testing for CF before or during pregnancy
see onenote
gives individuals and couples info about their risk of having a child with a genetic conditions
CF carrier screening recommended in Australia and US
Alleles used for carrier testing which will identify 80% of carriers
see onenote
Direct to consumer testing
see onenote slides
genetic testing that are marketed directly to consumers via tv, advertisements, internet
provides access to a person’s genetic info without necessarily involving a doctor or insurance company in the process
Genetic screening and testing services Victoria
see onenote
Adult: presymptomatic
- Huntington’s (at-risk families)
- colorectal cancers
Predictive and pre-symptomatic testing (PT) for genetic disorders
see onenote
Predictive testing
- Predicting if anyone in the general public is likely to develop a disease e.g. heart disease
Presymptomatic
- Applies to late onset disease that are occurring in the family
- Testing a family member to see if they have the mutation before they develop the symptoms e.g. Huntington’s
Huntington’s Disease
see onenote slides
- autosomal dominant
- 4p16.3 triplet repeat disorder
- CAG repeat
- inevitably fatal
clinical symptoms:
- progressive neurodegenerative disorder
- movement disorders
- dementia
- weight loss
- psychiatric disturbances
- difficulty with speech and swallowing
information re testing
see onenote
Pre-test protocol
- Sort out how you might react to a mutation positive test or if you don’t have the mutation
- Relationship to siblings who may or may not have the mutation
- Regardless of test result outcome, they do follow up counselling
Higher suicide rates for people who didn’t actually have the Huntington’s mutation
- Had been reckless with their lives since they initially thought they have the mutation since it runs in the family
Uptake rate - PT testing
see onenote
predicted over half would access predictive testing but actual uptake rates much lower
Low uptake rate for counselling
No cure, can delay onset of symptoms in mouse by keeping them physically and mentally active
Genetic testing and treatment - breast cancer
see onenote slides
- Oncotype DX test uses a sample of breast tissue to analyse a group of 21 genes
- testing breast cancer for receptors
Treatment
- hormone treatment
- aromatase inhibitors
