5.3 Disorders of the Basal Ganglia: Huntington’s Disease Flashcards
Describe the mode of genetic inheritance of Huntington’s
Autosomal dominant (it is a hunter, after all…)
Chorea word origin
Khoros -> dancing in chorus -> dance-like
Describe physical symptoms of Huntington’s disease
- Chorea
- Loss of coordination/balance
- Slurred speech
- Dysphagia
Describe cognitive symptoms of Huntington’s disease
- Forgetfulness
- Difficulty making decisions
Describe emotional changes in Huntington’s disease
- Hostility (HUNTington’s)
- Disinterest in life
Describe the change in the Huntington gene that leads to Huntington’s disease. How does this affect the Huntington protein?
- Lengthened CAG repeat in Huntington’s gene
- Leads to increased length of Huntington protein upon translation
Which basal ganglia pathway is affected FIRST in Huntington’s disease (eventually, both are)
Indirect pathway initially.
Describe the pathophysiology of Huntington’s
- Loss of medium spiny neurons from caudate (and, later, putamen).
- Affects indirect pathway first
- Cortical atrophy
On which arm of which chromosome is HTT (Huntingtin gene) located?
Short arm of chromosome 4 (otherwise known as 4p).
What is the normal number of CAG repeats found in the HTT gene?
26 or fewer
How many CAG repeats in the HTT gene are required for “HD-causing” alleles. What is the range for “at risk” vs full-penetrance
- 36 or more is HD-casuing
- 36-39 is at risk
- 40+ is full penetrance
Do heterozygotic/homozygotic Huntington’s disease have different ages of onset?
No. They do naht.
What is the function of Huntingtin?
Regulates mRNA transcription.
How many CAG repeats on HTT for “intermediate” range?
27-35
Describe the cis-acting factor that effects Huntington’s disease severity (affect gene expression only in the same chromosomal allele)
- Interrupted CAG repeat (where there is a CAA in the penultimate repeat); increased stability, more common
- Uninterrupted; less stable, less common