Genetics in Cardiology

Question 1

What are common CHD in Down syndrome?

Answer 1

• Atrioventricular septal defect (most common)
• VSD
• ASD
• PDA

Question 2

What causes Downs syndrome?

Answer 2

Trisomy 21

Question 3

The overexpression of what two genes can cause heart defects?

Answer 3

DSCAM and COL6A2

Question 4

What is the scientific term for Di George syndrome

Answer 4

22q11.2 deletion syndrome

Question 5

What abnormalities are commonly present in individuals with DiGeorge syndrome?

Answer 5

CATCH-22

• Cardiac abnormalities
• Abnormal facies
• Thymic aplasia
• Cleft palate
• Hypothyroidism

Question 6

What are the common cardiac abnormalities in DiGeorge syndrome?

Answer 6

• Tetralogy of Fallot
• Interruption of aortic arch
• VSD

Question 7

What can cause DiGeorge syndrome in patients who do not have a deletion?

Answer 7

Mutations in TBX1 (transcription factor)

Question 8

What is hypertrophic cardiomyopathy?

Answer 8

• Thickening of muscle in the heart resulting in disorganised myocytes and fibrosis
• Transmitted in an autosomal dominant way
• Cardiac B myosin heavy chain defect most likely cause
• Long QT (delays in repolarisation)
• Present in about 0.2% of population

Question 9

What is locus heterogeneity?

Answer 9

Defects in more than one gene causing phenotype

Question 10

What is considered a long QT interval?

Answer 10

Exceed 99th percentile

Question 11

What three genes account for around 2/3rds of cases around long QT?

Answer 11

• SCN5A (Na+ channel)
• KCNQ1 (K+)
• KCNH2 (K+)

Question 12

What is allelic heterogeneity?

Answer 12

Different mutations in the same gene can cause the same disease

Question 13

What does a mutation the SCN5A Na+ channel cause?

Answer 13

Na+ channel to stay open which causes too much sodium going into the cell making it very difficult for the K+ channel to repolarise

Question 14

What is penetrance

Answer 14

The proportion of individuals carrying a particular variant (or allele) of a gene that also express an associated trait

Question 15

What is familial hypercholesterolemia?

Answer 15

• 1 in 500

- High concentration of serum LDL cholesterol (total cholesterol > 7.5mM)

Question 16

What is the simon broome criterea?

Answer 16

• A method of diagnosing familial hypercholesterolemia
• Cholesterol >7.5mM (LDL>4.9mM)
• Plus either Tendon xanthelasma in patient or 1st/2nd degree relative
• or FH of MI
• DNA confirmation
• FH of cholesterol >7.5mM in 1st/2nd degree relative

Question 17

What kind of mutations can cause familial hypercholesterolemia?

Answer 17

LDL receptor >1000 different mutations
- Not synthesised 
- Not transported properly to cell membrane 
- Not bind LDL properly 
- Not internalised properly 
- Not recycled properly 
ApoB - Arg3500Gln 
LDL receptor associated protein - null mutations 
PCSK9 - Asp374Tyr

Question 18

What medications are generally used to treat familial hypercholesterolemia?

Answer 18

Statins

Question 19

What is cascade testing?

Answer 19

Cascade screening is a mechanism for identifying people at risk for genetic condition by a process of systemic family tracing