Neurogenetics

Question 1

What mode of inheritance is Duchenne muscular dystrophy?

Answer 1

X-linked recessive

Question 2

What mode of inheritance is Huntington’s disease?

Answer 2

Autosomal dominant

Question 3

What mode of inheritance is Spinal muscular atrophy?

Answer 3

Autosomal recessive

Question 4

What mode of inheritance is Alzheimer’s?

Answer 4

Polygenic or multifactorial

RARELY autosomal dominant

Question 5

When is the onset of Duchenne’s muscular dystrophy?

Answer 5

Childhood

Question 6

When is the onset of Huntington’s Disease most common?

Answer 6

30-50’s

Question 7

How does Duchenne Muscular Dystrophy present?

Answer 7

Delay in motor development
Muscle weakness @ 3-4 y/o
- Gower’s sign (using arms to get up from knees)
- Toe walking
- Exaggerated lumbar lordosis
Calf hypertrophy

Question 8

What gene has mutations in Duchenne muscular dystrophy?

Answer 8

Dystrophin gene

Question 9

What does the dystrophin protein do?

Answer 9

Connects actin filaments, needed for muscle contraction

Question 10

What are the two types of mutation in the select gene in Duchenne muscular dystrophy?

Answer 10

70% - Large scale deletion of dystrophin gene

30% - Point mutation, small insertion & deletion

Question 11

How is Duchenne muscular dystrophy diagnosed?

Answer 11

• Raised CK (screening)
• Molecular genetic testing (diagnostic)
• Electromyography (EMG)
• Muscle biopsy (diagnostic) - not common

Question 12

What is the inheritance pattern of limb girdle muscular dystrophies?

Answer 12

Autosomal recessive

Question 13

Does Duchenne muscular dystrophy only effect men?

Answer 13

Yes

Question 14

What is a common differential diagnosis for Duchenne muscular dystrophy?

Answer 14

Autosomal recessive limb girdle muscular dystrophy

Question 15

How is Huntington’s characterized?

Answer 15

Involuntary movements that can effect limb, trunk and face

Question 16

What cognitive effects can Huntington’s have?

Answer 16

Progressive dementia
- Progress to severe dependency and death over 15-20 yrs

Question 17

What are some late signs of Huntington’s?

Answer 17

• Rigidity
• Bradykinesia
• Weight loss
• Inability to walk
• Trouble speaking & swallowing
• Behavioral changes

Question 18

What physical changes can be observed in the brain of a Huntington’s patient?

Answer 18

Flattening of the lateral walls of the lateral ventricles

Question 19

What genetic mutation causes Huntington’s?

Answer 19

Pathological expansion of CAG trinucleotide

Question 20

What does the CAG trinucleotide code for?

Answer 20

Production of glutamine which is toxic to some cell types within brain

Question 21

What gene is mutated in spinal muscular atrophy?

Answer 21

SMN-1

Question 22

How does spinal muscular atrophy present?

Answer 22

Muscle weakness & wasting
- Proximal skeletal muscles
- Respiratory muscles

Due to loss of anterior horn cells and lower motor neurons

Question 23

How can progression of spinal muscular atrophy be halted?

Answer 23

By binding a synthetic oligonucleotide containing exon 7 to the neighboring SMN2 gene

Question 24

What is the underlying pathology of Alzheimer’s?

Answer 24

Loss of cortical neurons

AND

Abnormal deposition of proteins within and outside of cells

Question 25

What are senile plaques in azlheimers?

Answer 25

extracellular protein deposits containing amyloid B protein

Question 26

What genes are effected in the rare autosomal dominant form of Alzheimer’s?

Answer 26

APP gene
Presenilin 1 & 2

Question 27

What does the ApoE4 gene do in relation to Alzheimer’s?

Answer 27

Predisposes to Alzheimer’s