Autosomal Dominant Disorders Flashcards
List 7 autosomal dominant disorders.
1 - Dominant otosclerosis.
2 - Familial hypercholesterolaemia.
3 - von Willebrand disease.
4 - Marfan syndrome.
5 - Huntington disease.
6 - Familial adenomatous polyposis.
7 - Neurofibromatosis.
Briefly describe the pathophysiology familial hypercholesterolaemia.
The number of LDL receptors in the liver are halved, so uptake is halved.
What is anticipation?
A phenomenon whereby as a genetic disorder is passed on to the next generation, the symptoms of the genetic disorder become:
- apparent at an earlier age
- more severe
with each generation.
Define penetrance.
The extent to which carriers of a disease express the phenotype.
Define Mendelian inheritance.
Inheritance of traits that are controlled by a single locus.
e.g. autosomal dominant / recessive inheritance are examples of Mendelian inheritance.
List 2 signs of neurofibromatosis.
1 - Skin café au lait patches.
2 - Multiple neurofibroma (nerve sheath tumour).
What is age-dependent penetrance?
List 2 examples of diseases that often show age-dependent penetrance.
A delay in the onset of a genetic disease.
1 - Huntington disease.
2 - Breast cancer (mutated BRCA1 gene).
Give an example of a genetic disorder that shows incomplete penetrance.
Neurofibromatosis.
Define reduced / incomplete penetrance.
A condition is said to show incomplete penetrance when some individuals who carry the pathogenic variant express the associated trait while others do not.
List 3 genetic phenomena that can make a person appear to not have an autosomal condition when in fact they have the genotype.
1 - Incomplete penetrance.
2 - Age-dependent penetrance.
3 - Variation in expression.
Give an example of a disease of which new mutations cause the disorder in the majority of patients.
Achondroplasia.
Why do new mutations increase with paternal age?
Because higher mutation rates in males are related to a greater number of germ cell divisions.
What causes anticipation?
- Unstable, expanding trinucleotide repeat mutations.
- The severity / age of onset increase with the number of these repeats.
What do myotonic dystrophy, fragile X syndrome and Huntington disease have in common?
- They are all caused by trinucleotide repeats:
- Myotonic dystrophy = CTG.
- Huntington disease = CAG.
- Fragile X syndrome = CGG.
List 3 characteristics of an autosomal dominant inheritance pattern.
1 - Affected people in each generation.
2 - Both males and females affected in equal numbers.
3 - All forms of transmission seen.
