Genetics in Cardiology Flashcards
what are Common Cardiology defects in downs syndrome?
atrial septal defect
ventricular septal defect
atrioventricular canal defect
patent ductus arteriosus
what is the overall effect of cardiology defects in down’s syndrome?
mixing of oxygenated blood with deoxygenated blood making the system less efficient
what genetic defect causes downs?
trisomy of chromosome 21
how do you find out what causes the heart defects in people suffering from downs syndrome?
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
what gene usually predisposes heart defects in people with downs syndrome?
DSCAM on chromosome 21
what are genes DSCAM and COL6A2 involved in?
cell migration and adhesion
involved in causing heart defects in people suffering from downs syndrome
what are there abnormalities caused by 22q11.2 deletion syndrome?
CATCH-22 cardiac abnormal faces thymic aplasia cleft palate hypothyroidism
what cardiac abnormalities arise from 22q11.2 deletion syndrome?
tetralogy of fallot
interruption of the aortic arch
ventricular septal defects
how does 22q11.2 deletion syndrome occur?
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
how does 22q11.2 occur without deletion?
Mutaion on TBX1
can be base substitution- missence
can be deletion of amino acid- nonsense
What is TBX1?
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
how does too low or too high TBX1 prevent transcription?
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
what is hypertrophic cardiomyopathy?
ticketing of heart walls and inter ventricular septum
the thickness is disorganised, fibrotic as if scarred
how is hypertrophic cardiomyopathy inherited?
autosomal dominant manner
both males and females affected in every generation
what is locus heterogeneity?
defects in more than one gene but still in a single gene
how many different genes cause hypertrophic cardiomyopathy?
11 different genes
how is hypertrophic cardiomyopathy seen on an ECG? what causes this?
- long QT interval
- delay in repolarisation of cardiac cells, mutations in K channels resulting in long QT interval = issue with sodium channel
what do loss of function mutations affect?
can affect the way a portion of a channel is embedded in a membrane
also affect the cytoplasmic loop within the cell
define allelic heterogeneity
different mutations in the same gene all leading to a condition
which channel can be affected by allelic heterogeneity?
KCNQ1 channel and hence cant pump K out of the cell
what is an example of a gain of function mutation?
SCN5A
sodium channel stays open
what is Penetrance?
not everyone with a mutation will have any symptoms
why is it important to identify if individuals have mutations with reference to drugs?
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
what is familial hypercholesteraemia?
high serum cholesterol in blood
associated with morbidity at a young age
xanthoma- deposits
what is the Simon Broome Criteria for familial hypercholesteraemia?
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
how is familial hypercholesteraemia inherited ?
autosomal dominant manner
describe what a compound heterozygote is
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
what types of genes are affected in familial hypercholesteraemia?
genes in pathway controlled with removing cholesterol from the blood
LDL-receptor pathway
what is treatment for familial hypercholestermia? what is the issue with this treatment?
once you identify a family member who has the condition you can treat the disorder with statins
-not everyone responds to statins
what is cascade testing?
if a mutation is identified in a family you should then test other members of the family
