Genetics in Cardiology

Question 1

What are the common defects in Downs Syndrome?

Answer 1

• atrioventricular septal defect
• ventricular septal defect
• patent ductus arteriosus

Question 2

What is the genetic defect in Downs Syndrome?

Answer 2

trisomy 21

Question 3

What is a partial trisomy 21?

Answer 3

• extra material added to the q arm (long arm) of the chromosome
• rearrangement of p arm (short arm) of chromosome
• rare

Question 4

What is Di George Syndrome also known as?

Answer 4

22q11.2 deletion syndrome

Question 5

What are the consequences of Di George Syndrome?

Answer 5

(CATCH-22)

• cardiac abnormalities
• abnormal facies
• thymic aplasia
• cleft palate
• hypothyroidism

Question 6

What are the cardiac abnormalities associated with Di George Syndrome?

Answer 6

• interruption of aortic arch
• teratology of fallot
• ventricular septal defect

Question 7

Where do mutations commonly arise in Di George Syndrome?

Answer 7

mutations in TBX1

Question 8

What are pleiotropic effects?

Answer 8

1 gene influencing several unrelated traits

Question 9

What defines a long QT on an ECG?

Answer 9

if it exceeds the 99th percentile

Question 10

What are the basics of autosomal dominant inheritance?

Answer 10

• every generation affected
• males and females transmit
• mutation of one allele needed to be affected

Question 11

What are the basics of autosomal recessive inheritance?

Answer 11

• alternate generations affected
• males and females transmit
• mutations in both alleles needed to be affected

Question 12

What are consanguinous families?

Answer 12

Families all from the same ancestor

Question 13

How does penetrance differ from variable expression?

Answer 13

• variable expression is when an individual shows certain characteristics from a range of possible ones
• penetrance is when many individuals have the condition but to different severities which results in different phenotypes

Question 14

What is locus heterogenicity?

Answer 14

Mutations in different genes that cause the same phenotype

Question 15

What is a first degree relative?

Answer 15

Someone who shares 50% of your genes

Question 16

What is a second degree relative?

Answer 16

Someone who shares 25% of your genes

Question 17

What can cause a long QT?

Answer 17

• K+ channelopathy
• loss of function mutation
• not enough K+ leaving the cell giving a delayed repolarisation

Question 18

What is allelic heterogenecity?

Answer 18

When different mutations in the same locus result in the same phenotype

Question 19

What is compound heterozygosity?

Answer 19

An individual who has 2 or more heterogeneous recessive alleles on a particular locus that can cause genetic disease in a heterozygous state

Question 20

What can happen if there is a mutation in the LDL receptor?

Answer 20

• LDL not synthesised
• LDL not transported properly to the cell membrane
• LDL not bound properly
• LDL not internalised properly
• LDL not recycled properly

Question 21

Describe what different mutations to PCSK9 can result in

Answer 21

• gain of function mutation: high LDL-C

- loss of function mutation: low LDL-C

Question 22

What effect does inclisiran have on PCSK9 mutations?

Answer 22

• enters cell and blocks PCSK9 messenger RNA which contains instructions from the genes for making PCSK9
• more available LDL-C receptors and lower LDL-C levels in the blood

Question 23

Describe gain of function mutations

Answer 23

• Na+ channel stays open
• too much Na+ goes into cell
• constant depolatisation, difficult to repolatise