L21 Genetic Testing 2

Question 1

Testing late in pregnancy

Answer 1

see onenote

Question 2

Testing after birth - Guthrie spots

Answer 2

see onenote

• PKU, CF, hypothyroidism
• first condition screened was for PKU
• in Victoria, screens for 25 conditions

Question 3

Neonatal screening

Answer 3

see onenote

Question 4

Guthrie cards

Answer 4

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

Question 5

PKU

Answer 5

Phenylketonuria

• 1:12,000 in newborns
• phenylalanine hydroxylase gene PAH gene
• chromosome 1
• autosomal recessive
• variable expression depending on mutation and quantity of enzyme

Question 6

Metabolism of phenylalanine

Answer 6

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

Question 7

PKU - treatment

Answer 7

• diet low in phenylalanine and supplemented with tyrosine
• controversy how long diet is maintained
• diet resumed prior to and during pregnancy

Question 8

Screening neonates for Cystic fibrosis

Answer 8

• 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

Question 9

Newborn screening - CF (correlates to two slides)

Answer 9

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

Question 10

CFTR mutation types

Answer 10

see onenote

currently 2019 mutations listed in CFTR mutation database

Question 11

Cystic fibrosis - F508del

Answer 11

see onenote

PCR region of exon 10 with p.F508 del mutation to detect deletion on gel

Question 12

Sweat test

Answer 12

see onenote

- testing for Cl- concentration

Question 13

Victorian study: 1998 - 2008

Answer 13

see onenote

Question 14

Childhood testing - paternity testing

Answer 14

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

Question 15

Childhood testing - late onset diseases

Answer 15

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

Question 16

Carrier testing for CF before or during pregnancy

Answer 16

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

Question 17

Alleles used for carrier testing which will identify 80% of carriers

Answer 17

see onenote

Question 18

Direct to consumer testing

Answer 18

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

Question 19

Genetic screening and testing services Victoria

Answer 19

see onenote

Adult: presymptomatic

• Huntington’s (at-risk families)
• colorectal cancers

Question 20

Predictive and pre-symptomatic testing (PT) for genetic disorders

Answer 20

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

Question 21

Huntington’s Disease

Answer 21

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

Question 22

information re testing

Answer 22

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

Question 23

Uptake rate - PT testing

Answer 23

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

Question 24

Genetic testing and treatment - breast cancer

Answer 24

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