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Flashcards in Neurogenetics Deck (26)
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1
Q

what is Duchenne muscular dystrophy?

A

X linked recessive condition causing dystrophin deficiency

results in progressive delay in motor development

2
Q

life span of Duchenne muscular dystrophy?

A

onset of weakness around 3-4 years in girdles
wheelchair bound by 10-12
death from involvement of resp and carido muscles

3
Q

characteristic appearance of Duchenne muscular dystrophy?

A

characteristic posture = large lumbar lordosis
calf hypertrophy
gowers sign
toe walking

4
Q

how is DMD diagnosed?

A
characteristic signs
raised serum CK
electromyography
muscle biopsy
molecular genetic testing (screen for deletions)
5
Q

how are carriers tested for mutations?

A

identify mutation in affected boy
test for mutation in female relatives
female carriers of known DMD mutations can be offered pre-natal testing

6
Q

what is huntington disease?

A

autosomal dominant progressive neurological disorder causing involuntary movements, dementia and progression to severe dependency and death over 15-20 years
onset usually 30-50

7
Q

early clinical signs of huntingtons?

A
clumsiness
agitation
irritability
apathy
anxiety
disinhibition
delusions/hallucinations
abnormal eye movements
depression
8
Q

later clinical signs of huntingtons?

A
dystonia
involuntary movements
trouble balancing and walking
trouble with activities requiring dexterity
slow involuntary movements
difficulty initiating movement
inability to control speed and force of movement
weight loss
speech difficulty
stubbornness
9
Q

late clinical signs of huntingtons?

A
rigidity
bradykinesia
severe chorea
serious weight loss
inability to walk
inability to speak
swallowing problems
inability to care for self
10
Q

huntingtons causes atrophy of what?

A

caudate nucleus

- shows up on imaging

11
Q

what is the molecular genetic defect in Huntingtons?

A

too many repeats of CAG codon within the huntington gene

normal = up to 35, 36+ = huntington disease

12
Q

what does CAG codon code for?

A

glutamine

13
Q

huntington shows what type of penetrance?

A

age dependant

14
Q

how is predictive testing used in huntingtons?

A

informed consent due to implications of knowing that you have it (work, finances, emotional etc) despite there being no treatment
pre-natal and pre-gestational testing used for carriers who want to have children

15
Q

what is spinal muscular atrophy?

A

autosomal recessive disorder causing progressive loss of anterior horn cells in spinal cord and brain stem nuclei

16
Q

features of spinal muscular atrophy?

A

hypotonia
proximal muscle weakness
tongue fasciculation
variable age of onset and rate of progression

17
Q

deficiency of what causes symptoms in SMA?

A

SMN protein

18
Q

what is SMN protein?

A

protein made by SMN genes
usually 2 SMN1 genes and 2 SMN2 genes in each cell
spinal muscular atrophy = mutation/deletion of both SMN1 genes
(carrier = mutation/deletion of 1)

19
Q

how is SMN1 deficiency corrected?

A

altered splicing of mRNA translated from SMN2 gene
binding of synthetic oligonucleotide onto SMN2 mRNA results in retention of exon 7 in SMN2 mRNA
(only difference between SMN1 and SMN2 mRNA is the presence of exon 7, so altered splicing basically makes synthetic SMN1 mRNA and therefore SMN protein)

20
Q

what is Alzheimer disease?

A

most common cause of dementia
can also cause pre-senile dementia
genetic heterogeneity
shows clustering in some families

21
Q

what is the pathology in alzheimers?

A
loss of cortical neurones
neurofibrillary tangles (aggregates of hyperphosphorylated tau protein) (intracellular)
senile plaques (extracellular)
22
Q

what are senile plaques?

A

extra cellular protein deposits containing amyloid Beta protein

23
Q

is there any genetic component to alzheimers?

A

in some cases
autosomal dominant in 5-10% (generally only in early onset cases)
linked to down syndrome

24
Q

what causes autosomal dominant alzheimers?

A
APP mutations (chromosome 21)
presenilin 1 (chromosome 14)
presenilin 2 (chromosome 1)
25
Q

what is apolipoprotein E?

A

protein involved with fat metabolism
associated with Alzheimer disease
polymorphic (has 3 forms resulting from 3 alleles)
- e4 (55% get Alzheimers)
- e3
- e2
only e4 is considered to predispose to Alzheimer disease

26
Q

genetic link in MS?

A

multifactorial
no real definite link but clustering is seen in families
- higher concordance in monozygotic twins
more common in people with certain MHC haplotypes