Genetics

Question 1

In family tree what is:
1) square
2) circle
3) coloured in?

Answer 1

1) Male
2) Female
3) Disease

Question 2

What does x linked mean in regards to male transmission?

Answer 2

NOOOO male to male transmission

Question 3

If a male transmits onto a male it must be what?

Answer 3

Dominant

Question 4

What are the roles of genetics in repro medicine?

Answer 4

• Pre-conception counselling
• Early pregnancy screening
• Down syndrome screening
• Anomaly scan follow up
• Neonatal screening

Question 5

What is involved in targeted screening in preconception/early preg?

Answer 5

• Family history – AD / AR/ XL
• Previous obstetric history (loss/miscarriages could be a clue of an underlying genetic abnormality)
• Population carrier screening - AR or XL

Question 6

What is Gowers sign a classic sign of?

Answer 6

Muscle weakness-treat as emergency in young children-classic sign of Duchennes MD

Question 7

What does a mutation in haemoglobin gene (HbS) cause?

Answer 7

Sickle cell disease

(Being a carrier of SCD protects from malaria-it is a autosomal recessive condition)

Question 8

What are some potential complications of sickle cell disease?

Answer 8

• Stroke (overt & silent)
• Cerebrovascular disease (Moyamoya)
• Retinopathy
• Hearing loss/balance problems
• Asthma
• Acute chest syndrome
• Sleep apnoea
• PE

Question 9

What are the options for early detection & treatment in reproduction?

Answer 9

Pre-implantation genetic diagnosis: PGT-M (available on NHS for 1st child)
Prenatal diagnosis
NIPT- non-invasive prenatal testing

Question 10

What are some reproductive choices for inherited/known disease?

Answer 10

• Remain childless/adopt
• Gamete donation

Question 11

How is prenatal diagnosis carried out?

Answer 11

Chorionic villus sampling

Test for what they are concerned about but also check the chromosomes

Question 12

What is an excellent screening test for trisomies 21, 18 & 13?

Answer 12

Non-invasive prenatal testing/diagnosis- In the plasma is DNA leaked from both mother & foetus-find cell free foetal DNA-look for conditions

Question 13

What are some advantages of non invasive prenatal testing/diagnosis?

Answer 13

• Low false positive rate gives potential to avoid an invasive test which carries a risk of miscarriage
• Clarity of reported results - low chance or high chance of aneuploidy

Question 14

What are the limitations of non invasive prenatal testing/diagnosis?

Answer 14

• May be false negative or no result with a low fetal fraction
• May be a false positive with ‘vanishing’ twin, maternal cancer or placental mosaicism

Question 15

What are the ways that abnormal scans are investigated?

Answer 15

• Chromosomal microarray
• Gene panel e.g. skeletal dysplasia (Quick, targeted interpretation)
• Prenatal exome sequencing (Interpretation has to be phenotypically driven, Slower, more expensive)

Question 16

What is checked for in Newborn bloodspot screening test (Heel prick test)?

Answer 16

• SCD
• CF
• Congenital Hypothyroidism
• Phenylketonuria
• MCADD

Question 17

How is a seriously ill neonate investigated?

Answer 17

• Targeted testing
• Rapid trio-whole exome or whole genome sequencing

(Time intensive but cost-effective if case selection is good)

Have to sift & filter to find significant variants