Genetics in cardiology

Question 1

Common defects in Down syndrome

Answer 1

• Atrioventricular septal defect
• Ventricular septal defect
• Atrial septal defect
• Patient ductus arteriosus

50% have heart defects

Question 2

Genes that cause heart defects

Answer 2

Can have too much of a particular gene - DSCAM and COL6A2 - these two in combination cause heart defects

22q11.2 deletion syndrome (George syndrome) - defects with too little of gene

Question 3

These patients have abnormalities - what are they?

22q11.2 deletion

Answer 3

• Cardiac
• Abnormal faces
• Thymus gland problems - thymic aplasia
• Cleft palate
• Hypothyroidism

(CATCH-22)

Cardiac issues - interruption of aortic arch, tetralogy of fallot, ventricular septal defect

Question 4

Hypertrophic cardiomyopathy - phenotype

Answer 4

• Increased muscle thickness
• Disorganised mycoytes
• Fibrosis

Autosomal dominant - males and females equal chance and both can transmit onto next generation

Not all patients have disease in same gene - locus heterogeneity (11+ genes associated)
Exercise can cause sudden death

Question 5

Long QT

Answer 5

Exceeds 99th percentile of normal population
Delay in repolarisation of cardiac muscle - not enough potassium goes out of the cell
Different mutations in the same gene can cause disease - allelic heterogeneity
Majority of mutations in inside of cell membrane near the potassium channel
Also one mutation which makes the sodium channel open for longer, again delaying depolarisation

Autosomal dominant

Question 6

Why is it important to identify specific mutation?

Answer 6

In QT prolongation the C-loop mutation group had a big improvement when prescribed BB, whereas the non C-loop mutation group didn’t have much improvement - not worth prescribing

Question 7

What are problems in familial hypercholesterolemia?

Answer 7

• Xanthoma (irregular yellow patch or nodule on skin from lipid deposition)
• Atherosclerosis

Question 8

What are mutations in LDL-receptor pathway?

Answer 8

Over 1000 different mutations
Not synthesised, not transported properly to cell membrane, not bind LDL properly, not internalised properly, not recycled properly

Question 9

Testing for gene

Answer 9

can test family who has relatives with LDL receptor mutation - cascade testing
This is in contrast to population screening

Question 10

What is penetrance?

Answer 10

Extent of degree a gene or group of genes is expressed in a phenotype of a person