Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ATU 1 > Neuro - Huntingtons disease > Flashcards

Neuro - Huntingtons disease Flashcards

1
Q

When was it classed as a separate class of disorders?

A

1990s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What was the first disease discovered?

A

Fragile X

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How many diseases have been currently identified?

A

18 - may be more

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Can trinucleotide repeats be inherited?

A

Yes - increased repeat size can be due to paternal transmission - ‘classic anticipation’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 8 clinical features of trinucleotide repeat disorders?

A

Almost all exhibit ataxia

  • Chorea which is involuntary movement
  • Dystonia - muscles contractions
  • Dysarthria - difficulty in speaking (due to muscles)
  • Akathisia - ‘inability to sit’ want to move
  • Seizure
  • Tremor
  • Dementia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Are trinucleotide repeat disorders degenerative?

A

Yes - progressively degenerative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does the larger the expansion mean?

A

The earlier the onset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the 2 types of triplet expansion?

A

Type 1 and 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the repeats in type 1?

A

Always CAG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the pathological threshold of type 1?

A

35-40 where above this is pathological

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the repeats in type 2?

A

Repeat codon varies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the pathological threshold of type 2?

A

100+ - larger than type 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which type is always translated?

A

Type 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which type is transcribed but not translated?

A

Type 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which type is autosomal dominant?

A

Type 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Is type 2 autosomal dominant?

A

No the inhertance varies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Are inclusions seen in type 1?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Are inclusions seen in type 2?

A

No

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Are type 1 neurodegenerative?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Are type 2 neurodegenerative?

A

Variable - often pleiotropic phenotypes

21
Q

How does gene expansion occur?

A

Previously thought through double-stranded break repair by homologous recombination, crossover or non-homologous end joining.

But now suggested loop formation from single-stranded repair where there are 3 models for loop incorporation into duplex DNA involving mismatch repair machinery

22
Q

What is the most common type 1 disease?

A

Huntington’s

23
Q

Is Huntington’s nuclear or cytoplasmic localized?

A

Cytoplasmic

24
Q

What is the normal CAG repeat in Huntington’s

A

3-34

25
Q

What is the expanded CAG repeat in Huntington’s?

A

36-121

26
Q

How first described Huntington’s disease and when?

A

George Huntington in 1872

27
Q

What is the prevalence of Huntington’s

A

4-10/100,000 - rare

28
Q

What are the clinical features of HD?

A

Initially minimal where patients can suppress/mask the irregular movements
Chorea in 90% of cases
Dysarthria, Bradykinesia, Dysphagia
Cognitive decline - loss of recent memory, difficulty concentrating and judgement errors and various psychiatric symptoms, changes in personality, aptahy, social withdrawl, depression, agitiation, mania, delusions, hallicinations or psychosis
Progressive to death with 15-20 years

29
Q

How long after onset is death in HD?

A

15-20 years due to respiratory failure but also infection/suicide

30
Q

What age is the age of onset in HD?

A

~40 years with repid onset

31
Q

Where are cells lost in HD?

A

Cerebral cortex and corpus striatum

32
Q

What are the neurotransmitters which are altered in medium sized spiny neurones HD?

A

GABA and enkephalin

33
Q

Where do you get distruped signaling from in HD?

A

Thalamus and motor cortex caused by impair communication to muscles

34
Q

Is Huntington’s autosomal dominant?

A

Yes it is genetic

35
Q

Which chromosome is Huntington’s found on?

A

Chromosome 4 locus IT15

36
Q

Which exon are the CAG repeats found?

A

1 - at N-terminus

37
Q

Are there known sporadic cases of HD?

A

Yes

38
Q

What else does the Huntington’s gene contain?

A

WW repeats and caspase cleavage sites

39
Q

Do we know the function of the protein in HD?

A

No it is unassigned

40
Q

Where is the polyglutamine repeat located in the protein?

A

Near the N-terminus

41
Q

What motifs does Huntington contain?

A

Number of HEAT-repeat motifs and nuclear export signal - implies ability to enter/leave the nucleus

42
Q

Which 4 components of the cell is WT Huntington’s associated with?

A

ER
MT
Mitochondria
Synaptic vesicles

43
Q

Where is the mutated form of Huntingon’s know to form aggregated in?

A

Cytoplasm and nucleus

44
Q

Which terminal of Huntington’s is found in neuronal intracellular inclusions?

A

N-terminal

45
Q

How is Huntington’s disgonosed?

A

Clinical assessment - neurological testing, motor imerisistence, uses Unified Huntingson’s Disease Rating Scale
Family history of HD
Neuroimaging - EEG/CT/MRI scans get changes in certain regions
Genetic screening - CAG length

46
Q

What is the treatment for HD?

A

Movement disorder medication e.g. tetrabenazine for chorea
Psychiatric disorder medication e.g. Tricyclic or SSRI antidepressants for depression, Haloperidol for psychosis and hallucinations, Phenothaizine or benzodiazepines for movement and anxiety and Lithium for mood swings

47
Q

What are HDAC? and how can they be used in HD?

A

Class of enzymes which allow histones to wrap the DNA more tightly preventing transcription
Mutant Huntingtin inhibits acetylation (acetyltransferase activity) of histones H3 and H4
HDAC inhibitors in HD - Works in mouse models and Selisistat has recently found to be safe in Phase II trial of HD

48
Q

Clues in the function of Huntingtin

A

Required during developement - K.O. mice die at 7.5 days
Interacts with several proteins involved in intracellular trafficking, vesicle endocytosis/membrane trafficking, and trancription/histone acetylation

ATU 1 (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions