Flashcards in Neurogenetics Deck (33):
1
What is the mode of inheritance of duchenne muscular dystrophy?
X-linked recessive
2
What is the progression of duchenne muscular dystrophy?
Delay in motor development
Pelvic and shoulder girdle weakness at 3-4 years
Wheelchair bound by 10-12 years
Death from involvement of resp and cardiac muscles in 20s
3
What is the characteristic posture in duchenne muscular dystrophy?
Accentuated lumbar lordosis due to weakness in pelvic girdle muscles
4
What will occur in the legs of boys with DMD?
Calf hypertrophy; no strength gained just hypertrophied
5
Which protein dysfunction is DMD due to?
Dystrophin
6
What is the mode of action of dystrophin?
Connects actin filaments to the proteins at the cell membrane
Muscle cells cannot renew themselves and so will degenerate
7
What mutations result in DMD?
Deletion of dystrophin gene in 70%
Point mutations, small insertions in remaining 30%
8
How is DMD diagnosed?
Motor developmental delay
Gower's sign
Toe walking
Raised CK
EMG
Muscle biopsy
Molecular genetic testing for deletions
9
What is the change of inheritance in a boy whose mother is a carrier?
1 in 2
10
Are all cases of DMD from familiar inheritance?
No - 30% of DMD are de novo mutations
11
What is the incidence of huntington's disease?
1 in 20,000
12
At what age is huntington's disease most likely to present?
Between 30 and 50
13
What are the characteristics of huntington's disease?
Involuntary movements
Dementia
Progression to severe dependence and death over 15-20 years
14
What is the mode of inheritance in huntington's disease?
Autosomal dominant
15
What is different about the inheritance of huntington's disease?
Age dependent penetrance
Displays genetic anticipation
16
What are the early clinical signs of huntington's disease?
Clumsiness
Agitation
Irritability
Apathy
Anxiety
Disinhibition
Delusions
Hallucinations
Abnormal eye movements
Depression
17
What are the later clinical signs of huntington's disease?
Dystonia
Chorea
Trouble with balance and walking
Trouble with manual dexterity
Slow voluntary movements
Difficulty initiating movement
Inability to control speed and force of movement
Wt loss
Speech difficulties
Stubbornness
18
What are the end stage signs of huntington's disease?
Rigidity
Bradykinesia
Severe chorea
Serious wt loss
Inability to walk
Inability to speak
Swallowing problems
Inability to care for oneself
19
What is the basic pathogenesis of huntington's disease?
Caudate atrophy
20
What is the genetic basis of huntington's disease?
CAG repeats which codes for glutamine - this has a neurotoxic effect
21
What is the basic pathogenesis of /spinal muscular atrophy?
Progressive loss of anterior horn cells in the spinal cord and brain stem nuclei
22
What are the signs/symptoms of spinal muscular atrophy?
Hypotonia
Proximal muscle weakness
Tongue fasciculation
23
What is the inheritance of spinal muscular atrophy?
Autosomal recessive
24
Which gene is affected in spinal muscular atrophy?
SMN1 which is required for the survival of lower motor neurones
25
Is there a treatment for spinal muscular atrophy?
Yes - synthetic oligonucleotide
26
What is alzheimer's disease?
Common cause of dementia; 50-70% of cases
Occurs in old age
27
What is the genetic basis of alzheimer's disease?
Genetic heterogeneity
28
What is the basic pathology of alzheimer's disease?
Loss of cortical neurones
Neurofibrillary tangles (intracellular)
Senile plaques (extracellular)
29
What are senile plaques?
Extracellular protein deposits containing amyloid beta protein which is a fragment of the product of the amyloid precursor protein gene on chromosome 21
30
What percentage of alzheimer's is autosomal dominant?
5-10%
Commonly seen in early onset alzhemiers
31
Which genes have been identified to cause autosomal dominant alzheimer's?
APP mutations on chromosome 21
Presenilin 1 on chromosome 14
Presenilin 2 on chromosome 1
32
Which apoprotein can predispose to alzheimer's?
ApoE4
33