Genetics of CNS disease

Question 1

What is the inheritance of duchenne’s muscular dystrophy?

Answer 1

x-linked recessive

Question 2

What is the inheritance of Huntingtons disease?

Answer 2

autosomal dominant

Question 3

At what age does weakness tend to begin with DMD?

Answer 3

3-4years

Question 4

Where does weakness in DMD usually begin?

Answer 4

pelvic and pectoral gigrdles

Question 5

What is the characteristic posture of a boy with DMD?

Answer 5

accentuated lumbar lordosis

Question 6

What is typically seen in the legs of patients with DMD?

Answer 6

calf hypertrophy

Question 7

What causes DMD?

Answer 7

deficiency of dystrophin

Question 8

What is the function of dystrophin?

Answer 8

connects contractile elements eg actin in muscle cell to proteins in the cell membrane

Question 9

What is the difference between DMD and BMD?

Answer 9

duchennes dont have dystrophin at all whereas BMD have a shortened version of the protein

Question 10

What is the most common genetic mutation in DMD?

Answer 10

large scale deletion of dystrophin gene in 70%

Question 11

Why is toe walking seen in patients with DMD?

Answer 11

shortening of their achilles tendon

Question 12

What are the investigations done fro DMD?

Answer 12

CK; EMG; muscle biopsy; genetic testiing

Question 13

When is the typical onset of Huntington’s?

Answer 13

between 30 and 50

Question 14

What are the early signs of Huntington’s?

Answer 14

clumsiness; agitation; irritabililty; apathy; anxiety; disinhibtion; delusions; abnormal eye movements; depression

Question 15

What are the later signs of Huntington’s?

Answer 15

dystonia; involuntary movements; slow voluntary movements; weight loss; speech difficulties; stubbornness

Question 16

What happens to the basal ganglia in Huntington’s?

Answer 16

caudate nucleus atrophy (and cerebral cortex)

Question 17

What is the genetic defect in HD?

Answer 17

increased CAG repeats

Question 18

What does CAG code for and why does excess repeats cause problems?

Answer 18

glutamine- too much is neurotoxic

Question 19

What happens to the Huntington gene as it is passed down?

Answer 19

increased exapnsions so decreased age of onset

Question 20

What is the pathology seen in Alzheimers?

Answer 20

loss of cortical neurones; protein deposits intracellular- neurofibrillary tangles and extracellular- senile plaques

Question 21

What are senile plaques?

Answer 21

extracellular protein deposits containing amyloid beta protein

Question 22

What is amyloid beta protein?

Answer 22

a fragment of the product of the amyloid precursor protein from chromosome 21

Question 23

What genetic condition is associated with early onset Alzheimers?

Answer 23

Down syndrome

Question 24

What mutations can cause autosomal dominant early onset Alzheimers?

Answer 24

APP mutations of chromosome 21; Presenilin 1- chromsoms 14 and Presenilin 2 on chromosome 1

Question 25

Which allele of apolipoprotein E predisposes to Alzheimers?

Answer 25

e4

Question 26

What is the concordance of MS in monozygotic twins vs dizygotic twins?

Answer 26

25% vs 3%