Genetics in Cardiology

Question 1

what are Common Cardiology defects in downs syndrome?

Answer 1

atrial septal defect
ventricular septal defect
atrioventricular canal defect
patent ductus arteriosus

Question 2

what is the overall effect of cardiology defects in down’s syndrome?

Answer 2

mixing of oxygenated blood with deoxygenated blood making the system less efficient

Question 3

what genetic defect causes downs?

Answer 3

trisomy of chromosome 21

Question 4

how do you find out what causes the heart defects in people suffering from downs syndrome?

Answer 4

look at DNA of people with downs syndrome
see the DNA make up of the chromosome
compare the DNA make up the chromosome with other people who have downs and hence start looking at the genes which cause heart problems

Question 5

what gene usually predisposes heart defects in people with downs syndrome?

Answer 5

DSCAM on chromosome 21

Question 6

what are genes DSCAM and COL6A2 involved in?

Answer 6

cell migration and adhesion

involved in causing heart defects in people suffering from downs syndrome

Question 7

what are there abnormalities caused by 22q11.2 deletion syndrome?

Answer 7

CATCH-22
cardiac 
abnormal faces
thymic aplasia 
cleft palate
hypothyroidism

Question 8

what cardiac abnormalities arise from 22q11.2 deletion syndrome?

Answer 8

tetralogy of fallot
interruption of the aortic arch
ventricular septal defects

Question 9

how does 22q11.2 deletion syndrome occur?

Answer 9

chromosome 22 has a long range of repeat
DNA recombination can occur in these genes which are repeated
rearrangement occurs: DeNovo, or when we carry the deletion

Question 10

how does 22q11.2 occur without deletion?

Answer 10

Mutaion on TBX1
can be base substitution- missence
can be deletion of amino acid- nonsense

Question 11

What is TBX1?

Answer 11

transcription factor
DNA binding factor looking for partner sequences of DNA and can regulate how much mRNA binds to sequence and how much protein is produced from the gene

Question 12

how does too low or too high TBX1 prevent transcription?

Answer 12

too high- cant find partner combined and cant cause transcription of genes
too low- dimerises to self and inactive dimeric form blocks heterodimer hence still preventing transcription of genes

Question 13

what is hypertrophic cardiomyopathy?

Answer 13

ticketing of heart walls and inter ventricular septum

the thickness is disorganised, fibrotic as if scarred

Question 14

how is hypertrophic cardiomyopathy inherited?

Answer 14

autosomal dominant manner

both males and females affected in every generation

Question 15

what is locus heterogeneity?

Answer 15

defects in more than one gene but still in a single gene

Question 16

how many different genes cause hypertrophic cardiomyopathy?

Answer 16

11 different genes

Question 17

how is hypertrophic cardiomyopathy seen on an ECG? what causes this?

Answer 17

• long QT interval
• delay in repolarisation of cardiac cells, mutations in K channels resulting in long QT interval = issue with sodium channel

Question 18

what do loss of function mutations affect?

Answer 18

can affect the way a portion of a channel is embedded in a membrane
also affect the cytoplasmic loop within the cell

Question 19

define allelic heterogeneity

Answer 19

different mutations in the same gene all leading to a condition

Question 20

which channel can be affected by allelic heterogeneity?

Answer 20

KCNQ1 channel and hence cant pump K out of the cell

Question 21

what is an example of a gain of function mutation?

Answer 21

SCN5A

sodium channel stays open

Question 22

what is Penetrance?

Answer 22

not everyone with a mutation will have any symptoms

Question 23

why is it important to identify if individuals have mutations with reference to drugs?

Answer 23

patients with mutations in C-loop then therefore B blockers struggle to reduce complications
if patients have mutations in transmembrane proteins B-blockers will have no effect on these patients

Question 24

what is familial hypercholesteraemia?

Answer 24

high serum cholesterol in blood
associated with morbidity at a young age
xanthoma- deposits

Question 25

what is the Simon Broome Criteria for familial hypercholesteraemia?

Answer 25

people have high cholesterol so how to determine if its familial:
studies of extended family
1st degree relative= child share 50% of information with
2nd degree= grandchild 25% of information is shared with

Question 26

how is familial hypercholesteraemia inherited ?

Answer 26

autosomal dominant manner

Question 27

describe what a compound heterozygote is

Answer 27

individuals with different mutations causing there disease/condition
when they pass on their genes the individual affected receives different mutations from each individual
hence they are more severely affected
no functioning genes in this pathway

Question 28

what types of genes are affected in familial hypercholesteraemia?

Answer 28

genes in pathway controlled with removing cholesterol from the blood
LDL-receptor pathway

Question 29

what is treatment for familial hypercholestermia? what is the issue with this treatment?

Answer 29

once you identify a family member who has the condition you can treat the disorder with statins
-not everyone responds to statins

Question 30

what is cascade testing?

Answer 30

if a mutation is identified in a family you should then test other members of the family