Genetics in pregnancy

Question 1

What are the different methods of sampling for genetic testing in antenatal care and when during the pregnancy can they be done ?

Answer 1

1. CVS - 11.5 to 14wks
2. Amniocentesis - from 16wks +
3. Fetal blood sampling - from 18+wks
4. Fetal DNA from maternal blood (NIPT) - 8+ wks

Question 2

What is the main problem associated with CVS ?

Answer 2

Confined placental mosaicisim

Question 3

What is the problem with amniocentesis ?

Answer 3

Poor tissue avaliability

Question 4

Is fetal blood sampling used often ?

Answer 4

No it is rarley used

Question 5

What is the problem with NIPT ?

Answer 5

Only limited analyses avaliable

Question 6

Define what a chromosome is

Answer 6

A package containing a chunk of a genome - that is it contains some of the organisms genes (hence why you have 46 to make up together all the genome)

Question 7

Define what the genome is

Answer 7

It is the whole of the genetic info of an organism i.e. all its genes

Question 8

Define what a gene is

Answer 8

It is a segment of DNA on a chromosome that describes how to make a certain protein

Question 9

What is the main test used to test the whole genome in genetics and give an example of the sort of mutation it is used to find

Answer 9

Array CGH - used to find bigger mutations such as chromosome changes e.g. DS, can be used for smaller mutations but not for things as small as point mutations

Question 10

What is the main genetic test used for very small mutations such as point mutations ?

Answer 10

FISH

Question 11

What is the problem with whole genome testing ?

Answer 11

You find millions of polymorphisms so need to distinguish these from the disease causing mutation

Question 12

Define a mutation

Answer 12

A genetic change which causes disease

Question 13

Define a polymorphism

Answer 13

A genetic variation that is not disease causing

Question 14

What factors would help indicate a genetic change is a mutation?

Answer 14

• Its de-novo
• Affects the known gene involved in the disease
• Previously reported in same phenotype

Question 15

What factors would help indicate a genetic change is a polymorphism?

Answer 15

• Normal parent has it
• Found in ‘‘empty’’ genetic region
• Previously reported as a polymorphism

Question 16

When would QF-PCR be used and why ?

Answer 16

If a baby is born and quick confirmation is needed to confirm they have a condition (this is a whole genome test so needs to be big mutations) e.g. to quickly confirm DS on birth in clinically suspected baby

Question 17

When do you do Array-CGH or chromsome analysis ?

Answer 17

1. When high risk of DS on screening
2. If fetal abnormality seen on screening
3. Parent has a balanced chromsomal rearrangement

Question 18

What is NIPT currently used for ?

Answer 18

• Sex determination
• Trisomy screening

Question 19

Mrs Pink comes to see you. She is 10 weeks pregnant. She has a son who is affected with Duchenne muscular dystrophy.

What genetic test would you offer ?

Answer 19

NIPT as can determine sex and ==> if any more testing needed

If male then CVS would be the next test due to date of pregnancy

If female no test needed as mutation is X-linked

Question 20

Mrs Blue comes to see you. She is 18 weeks pregnant. A detailed scan has shown that her baby has a cardiac defect: an AtrioVentricular Septal Defect (AVSD) that is commonly seen in Down syndrome

1. Reassurance
2. Serum Screening
3. Chorionic Villus Biopsy
4. Amniocentesis
5. Non-Invasive Prenatal testing

Answer 20

4 - Amniocentesis

Question 21

Mrs Blue comes to see you. She is 18 weeks pregnant. A detailed scan has shown that her baby has a cardiac defect: an AtrioVentricular Septal Defect (AVSD) that is commonly seen in Down syndrome.

1. Array CGH
2. Karyotype
3. Chromosome analysis
4. FISH for 21
5. DNA testing for a point mutation

Answer 21

1 - array-CGH

Question 22

What can array-CGH not detect?

Answer 22

Balanced chromsome abnormalities

Question 23

What does FISH detect ?

Answer 23

The presence or absence of specific DNA sequences on chromosomes

Question 24

Define a robertsonian translocation

Answer 24

2 acrocentric chromsomes stuck end to end

Question 25

Define what a reciprocal translocation is

Answer 25

Chromosome rearrangement invovlving exchange of chromosome segements between 2 chromosomes that do not belong to the same pair of chromosomes as eachother

Question 26

What will conception in parents with translocations result in ?

Answer 26

50% of conception will have either normal chromosomes or balanced translocation. Unbalanced products result in miscarriage, dysmorphic delayed child etc

Question 27

Mrs Roberts comes to see you. She is 10 weeks pregnant. She has a balanced reciprocal translocation between chromosome 4 and chromosome 9, that has a high risk of causing a liveborn child with multiple malformations. 1. Reassurance 2. Serum Screening 3. Chorionic Villus Biopsy 4. Amniocentesis 5. Fetal Blood Sampling

Answer 27

3 - CVS

Question 28

What is the risk of inheriting an x-linked disorder ?

Answer 28

It is 25%, unless the fetus is known to be male then it is 50%

Question 29

What is the risk of inheriting an autosomal dominant disorder?

Answer 29

50%

Question 30

What is the risk of inheriting an autosomal recessive disorder ?

Answer 30

25%

Question 31

What is pre-implantation genetic diagnosis (PGD) and who is it done for?

Answer 31

This is an IVF like technique which involves performing a genetic test on an embryo before re-implanting one with the ‘correct’ genotype The couple must be at risk of having a child with a serious genetic condition

Question 32

For what genetic conditions is PGD carried out for ?

Answer 32

Chomromosal abnormalities - mainly reciprocal & robertsonian translocations Single gene testing: 1. Autosomal recessive disorders - CF, beta-thalassaemia, sickle cell, spinal muscular dystrophy 2. Autosomal dominant disorders - myotonic dystrophy, huntingtons disease 3. X-linked diseases - fragile X-syndrome, haemophilia A, duchenne muscular dystrophy