Genetics in Cardiology Flashcards
What are the common defects in Downs Syndrome?
- atrioventricular septal defect
- ventricular septal defect
- patent ductus arteriosus
What is the genetic defect in Downs Syndrome?
trisomy 21
What is a partial trisomy 21?
- extra material added to the q arm (long arm) of the chromosome
- rearrangement of p arm (short arm) of chromosome
- rare
What is Di George Syndrome also known as?
22q11.2 deletion syndrome
What are the consequences of Di George Syndrome?
(CATCH-22)
- cardiac abnormalities
- abnormal facies
- thymic aplasia
- cleft palate
- hypothyroidism
What are the cardiac abnormalities associated with Di George Syndrome?
- interruption of aortic arch
- teratology of fallot
- ventricular septal defect
Where do mutations commonly arise in Di George Syndrome?
mutations in TBX1
What are pleiotropic effects?
1 gene influencing several unrelated traits
What defines a long QT on an ECG?
if it exceeds the 99th percentile
What are the basics of autosomal dominant inheritance?
- every generation affected
- males and females transmit
- mutation of one allele needed to be affected
What are the basics of autosomal recessive inheritance?
- alternate generations affected
- males and females transmit
- mutations in both alleles needed to be affected
What are consanguinous families?
Families all from the same ancestor
How does penetrance differ from variable expression?
- 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
What is locus heterogenicity?
Mutations in different genes that cause the same phenotype
What is a first degree relative?
Someone who shares 50% of your genes
What is a second degree relative?
Someone who shares 25% of your genes
What can cause a long QT?
- K+ channelopathy
- loss of function mutation
- not enough K+ leaving the cell giving a delayed repolarisation
What is allelic heterogenecity?
When different mutations in the same locus result in the same phenotype
What is compound heterozygosity?
An individual who has 2 or more heterogeneous recessive alleles on a particular locus that can cause genetic disease in a heterozygous state
What can happen if there is a mutation in the LDL receptor?
- LDL not synthesised
- LDL not transported properly to the cell membrane
- LDL not bound properly
- LDL not internalised properly
- LDL not recycled properly
Describe what different mutations to PCSK9 can result in
- gain of function mutation: high LDL-C
- loss of function mutation: low LDL-C
What effect does inclisiran have on PCSK9 mutations?
- 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
Describe gain of function mutations
- Na+ channel stays open
- too much Na+ goes into cell
- constant depolatisation, difficult to repolatise
