Neurogenetics

Question 1

What is the inheritance pattern in DMD?

Answer 1

x-linked recessive

however it is caused by new mutations in 1 in 3 boys

Question 2

What is the genetic defect in DMD?

Answer 2

large scale deletion of dystrophin gene in 70%

point mutations, small insertions and deletions in remaining 30%

Question 3

What is the inheritance pattern in Huntington’s disease?

Answer 3

autosomal dominant

Question 4

Describe the penetrance seen in HD and what this means.

Answer 4

age dependent penetrance (variable)

chance seems to decrease with age

Question 5

What is the normal Huntingtin gene vs pathogenic variant?

Answer 5

CAG-20
vs
CAG-42

Question 6

What does CAG code for?

Answer 6

glutamine

Question 7

Which condition involves loss of anterior horn cells in the spinal cord and brain stem nuclei?

Answer 7

spinal muscular atrophy

Question 8

Inheritance pattern of spinal muscular atrophy

Answer 8

autosomal recessive

Question 9

A deletion on chromosome 5 would result in which type of spinal muscular atrophy?

Answer 9

SMN1 deficiency

Question 10

What is the difference between SMN1 and SMN2? What does this mean for treatment?

Answer 10

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

Question 11

List some of the possible mutations seen in early onset Alzheimer’s disease.

Answer 11

Early onset = autosomal dominant
APP mutations - chromosome 21
presenilin 1 - chromosome 14
presenilin 2 - chromsome 1

Question 12

Which polymorphic apolipoprotein predisposes to alzheimer’s with some clustering in families?

Answer 12

Apo e4

Question 13

Which apolipoprotein has the highest frequency seen in AD?

Answer 13

Apo e3 (72%)

Question 14

Which apolipoprotein is associated with longevity?

Answer 14

Apo e2

Question 15

Which mutation is commoner in alzheimer’s - autosomal dominant or multifactorial forms?

Answer 15

commoner –> multifactorial forms

rare AD forms

Question 16

T/F: patients with no apolipoprotein e4 genotype are most likely to acquire Alzheimer’s.

Answer 16

false: no e4 –> 9% affected by 85

Question 17

The genotype for Alzheimer’s with highest penetrance is e4/e4 - T/F?

Answer 17

true

55% affected by 80

Question 18

Describe the damage to spinal cord in DMD.

Answer 18

there is no damage to spinal cord or nerves

Question 19

Which muscle component is destroyed in DMD?

Answer 19

sarcolemma

Question 20

Patient presents with gradually progressive hypotonia, proximal muscle weakness and tongue fasciculations. Ddx?

Answer 20

spinal muscular atrophy (progressive loss of anterior horn cells)

Question 21

What is the APP gene and where is it found?

Answer 21

amyloid precursor protein found on chromosome 21

Question 22

what is amyloid beta protein and where is it found?

Answer 22

a fragment of the APP gene, found in deposits in senile plaques in Alzheimer’s disease