Genetics in cardiology

Question 1

What are common defects in Down syndrome

Answer 1

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

Question 2

What causes Down syndrome

Answer 2

Trisomy 21

DSCAM and COL6A2 transgenics

Question 3

Discuss CATCH-22

Answer 3

22q11.2 deletion syndrome, or DiGeorge Syndrome, named CATCH-22 after symptoms:

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

Question 4

What cardiac abnormalities occur in CATCH-22 (22q11.2 deletion syndrome)(DiGeorge Syndrome)

Answer 4

• Interruption of aortic arch
• Tetralogy of Fallot
• Ventricular septal defect

Question 5

Discuss familial hypercholesterolemia

Answer 5

• High concentration of serum LDL cholesterol (total cholesterol>7.5mM)
• Xanthoma (cool wart like deposits of cholesterol)
• Atherosclerosis

Question 6

Discuss mutations in LDL-receptor pathway

Answer 6

• 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 7

Summary

Answer 7

• Effects of gene dosage
• Autosomal dominant/recessive
• Locus heterogeneity
• Allelic heterogeneity
• Compound heterozygosity
• Penetrance
• Cascade testing vs population screening