Huntingtons Disease

Question 1

What is Huntingtons disease?

Answer 1

Autosomal dominant, hereditary, Neurodegenerative Disease

Question 2

What the probability it’s passed onto offspring?

Answer 2

50%

Question 3

How can you characterise Huntingtons disease?

Answer 3

A cognitive behavioural and motor dysfunction.

Question 4

What is the faulty gene in huntingtons?

Answer 4

HTT gene (IT15)

Question 5

Where is Huntingtin gene located?

Answer 5

On chromosomes 4

Question 6

How many repeats are needed to cause Huntingtons?

Answer 6

36 or more

Question 7

What is the codon repeated in Huntingtons disease?

Answer 7

CAG- produces glutamines.

Question 8

What do the Huntington repeats produce?

Answer 8

Extra glutamine residues

Question 9

What are the stages of clinical progression in Huntingtons?

Answer 9

Pre-symptomatic
Predromal
Manifest

Question 10

What is the pre-symptomatic stage of Huntingtons disease?

Answer 10

Stage before symptoms show

Question 11

What is the predromal stage of Huntingtons disease?

Answer 11

When symptoms begin to appear

Question 12

What is the manifest stage of Huntingtons disease?

Answer 12

Stage with clear symptoms

Question 13

What three ways do Huntingtons symptoms show?

Answer 13

It affects:
Movement (usually first symptom)
Behaviour
Cognitive

Question 14

Name some physical symptoms of Huntingtons?

Answer 14

Motor deficits
Weight loss
Abnormal eye movement
Slurred speech
Incontinence
Involuntary movement

Question 15

What are the cognitive symptoms of Huntingtons disease?

Answer 15

Memory problems
Concentration problems
Emotional changes
Aggressive

Question 16

What grades are there of loss of medium spiny neurons in Huntingtons disease

Answer 16

0-4

Question 17

What’s grade 0/1 of loss of medium spiny neurons in Huntingtons?

Answer 17

Indistinguishable from a normal brain. Only selective loss of neurons in caudate nucleus and putamen

Question 18

What’s grade 2 of loss of medium spiny neurons in Huntingtons?

Answer 18

Enlargement of lateral ventricle, loss of cortico-striatal projection neurons. Severe striatal atrophy.

Question 19

What’s grade 3/4 of loss of medium spiny neurons in Huntingtons?

Answer 19

Severe HD cases with atrophy of the striatum and wide cell loss on other cortical, hippocampal cerebellum and hypothalamic regions.

Question 20

What happens when you have polyQ Huntingtin?

Answer 20

Forms an abnormal shape and subsequently aggregates forming inclusion bodies in neurons.

Question 21

What are inclusion bodies?

Answer 21

Collections of insoluble proteins (Huntingtons)

Question 22

What is loss of function (LOF)?

Answer 22

When mutant proteins are no longer able to perform normal functions.

Question 23

What is gain of function (GOF)?

Answer 23

Extra activity that a mutants proteins gains from mutation

Question 24

What is mtHTT and HTT?

Answer 24

Mutant Huntingtin and Huntingtin

Question 25

What does mtHTT do?

Answer 25

Inhibits gene transcription and also histone modification limiting transcription further.

Question 26

How does HD cause mitochondrial dysfunction?

Answer 26

Leads to enhanced sensitivity to mPTP, leading to pore opening a reduction in membrane potential and subsequent apoptosis.

Question 27

What is an example of Huntingtons LOF?

Answer 27

HTT blocks procaspase-9 by direct binding, when mutated this doesn’t occur leading to higher risk and susceptibility to apoptosis.

Question 28

What therapeutic strategies are there for Huntingtons?

Answer 28

Anti-sense oligonucleotide- allele selective drugs that bind to and target single poly-morphisms for degradation such as in Huntingtons.