Lecture 19 Part 2 - Huntington

Question 1

What is huntington Disease

Answer 1

a hereditary form of chorea first described in 1872

Question 2

What are the three features that distinguishes huntington disease

Answer 2

• hereditary nature
• tendency to insanity and suicide
• manifesting itself as a grave disease only in adult life

Question 3

What is the phenotype of huntington disease

Answer 3

• psychological impairment
• cognitive dysfunction
• physical impairment

Question 4

What is the prevalence of huntington disease

Answer 4

9.33/100 000

Question 5

What is the treatment of huntington

Answer 5

no effective treatment or cure

Question 6

What is the prognosis of huntington

Answer 6

fatal

Question 7

What is the mangement for huntington

Answer 7

• antidepressants, antipsychotics
• physical therapy and speech therapy
• tetrabenazine is a treatment for chorea but increases risk of suicide
• high calorie diet since they are always moving

Question 8

What gene causes the disorder

Answer 8

the huntingtin gene located on the short arm of chromosome 4, the gene is ~169000nt with 67 exons

Question 9

What causes huntington disorder

Answer 9

expansion of the CAG repeat in exon 1

Question 10

What is the mechanism of the disease

Answer 10

The expansion of the CAG region in exon 1 translates as a polyglutamine repeat in
the protein product
1. It is possible that the long RNA molecule is directly or indirectly toxic to neurons
2. It is possible the abnormal protein has a new function which is detrimental to
neurons

Question 11

What are the findings in huntington disease

Answer 11

• Neuropathological alterations are found widely throughout the brain.
• Atrophy is observed in the striatum and cerebral cortex
• The striatum control involuntary movement, cognition and the reward system
• The cerebral cortex is involved in memory, & movement

Question 12

What diagnostic testing is done for huntington disease

Answer 12

• Huntington is an autosomal dominant disease; one copy of the
  variant gene is sufficient to cause disease
• The enumeration of of the number of CAG repeats in exon one is
  used for a molecular diagnosis
• Not everyone is tested if there is already a family history pf the
  disease

Question 13

How are the number of CAG repeats significant

Answer 13

• </= 26 repeats are considered normal
• individuals with 26-35 repeats will not develop the disease but next generation may
• Individuals with 36-39 repeats may develop the disease (reduced penetrance) and the next generation may
• individuals with 40 or more will develop the disease (full penetrance) age of onset correlates with the number of repeats

Question 14

What is triplet repeat primed PCR

Answer 14

• PCR method that generates different sized amplicons due to multiple annealing sites
• will appear as a stuttering pattern on an electropherogram

Question 15

How do the primers in TRP PCR work

Answer 15

• one is labelled with a fluorophore and determines the specificity of the react as it anneals to a region flanking the repeat
• the second primer anneals to the flanking DNA sequence at the opposite end and binds randomly along the trinucleotide