Neurogenetics Flashcards
What is the inheritance pattern in DMD?
x-linked recessive
however it is caused by new mutations in 1 in 3 boys
What is the genetic defect in DMD?
large scale deletion of dystrophin gene in 70%
point mutations, small insertions and deletions in remaining 30%
What is the inheritance pattern in Huntington’s disease?
autosomal dominant
Describe the penetrance seen in HD and what this means.
age dependent penetrance (variable)
chance seems to decrease with age
What is the normal Huntingtin gene vs pathogenic variant?
CAG-20
vs
CAG-42
What does CAG code for?
glutamine
Which condition involves loss of anterior horn cells in the spinal cord and brain stem nuclei?
spinal muscular atrophy
Inheritance pattern of spinal muscular atrophy
autosomal recessive
A deletion on chromosome 5 would result in which type of spinal muscular atrophy?
SMN1 deficiency
What is the difference between SMN1 and SMN2? What does this mean for treatment?
SMN2 is identical to SMN1 mRNA but exon 7 is spliced out
this means that SMN1 deficiency can be corrected by altering the spicing of SMN2 mRNA
List some of the possible mutations seen in early onset Alzheimer’s disease.
Early onset = autosomal dominant
APP mutations - chromosome 21
presenilin 1 - chromosome 14
presenilin 2 - chromsome 1
Which polymorphic apolipoprotein predisposes to alzheimer’s with some clustering in families?
Apo e4
Which apolipoprotein has the highest frequency seen in AD?
Apo e3 (72%)
Which apolipoprotein is associated with longevity?
Apo e2
Which mutation is commoner in alzheimer’s - autosomal dominant or multifactorial forms?
commoner –> multifactorial forms
rare AD forms
T/F: patients with no apolipoprotein e4 genotype are most likely to acquire Alzheimer’s.
false: no e4 –> 9% affected by 85
The genotype for Alzheimer’s with highest penetrance is e4/e4 - T/F?
true
55% affected by 80
Describe the damage to spinal cord in DMD.
there is no damage to spinal cord or nerves
Which muscle component is destroyed in DMD?
sarcolemma
Patient presents with gradually progressive hypotonia, proximal muscle weakness and tongue fasciculations. Ddx?
spinal muscular atrophy (progressive loss of anterior horn cells)
What is the APP gene and where is it found?
amyloid precursor protein found on chromosome 21
what is amyloid beta protein and where is it found?
a fragment of the APP gene, found in deposits in senile plaques in Alzheimer’s disease
