Genetics

Question 1

What type of inheritance is Duchenne muscular dystrophy

Answer 1

X linked recessive

Therefore more common in males

Question 2

Describe the disease progression in DMD

Answer 2

Delay in motor development
Onset of weakness in pelvic and shoulder girdles age 3-4
Wheelchair bound by 10-12
Death by involvement of cardiac and respiratory muscles by 20s

Question 3

What are the classic physical signs of DMD

Answer 3

Posture - hips forward
Hypertrophy of the calves
Gower’s sign - walk hands up legs to stand
Toe walking

Question 4

What causes DMD

Answer 4

Due to fault in dystrophin protein - lack of it
Gene is on the X chromosome
This prevents muscle cells renewing themselves normally

Question 5

How do you diagnose DMD

Answer 5

Clinical signs - developmental delay, toe walking, Gower's 
Raised CK 
Electromyography  
Muscle biopsy 
Molecular genetic tests

Question 6

What is creatine kinase a test for

Answer 6

Non-specific for muscle disease

Leaks out of damaged muscle

Question 7

When is the usual onset of Huntington’s disease

Answer 7

Between 30 and 50 years old

Question 8

What type of inheritance does Huntington’s disease show

Answer 8

Autosomal dominant

Question 9

Is Huntington’s a progressive disease?

Answer 9

YES
Progressive physical and cognitive symptoms
Will go on to become severely dependant and then die

Question 10

What are the early clinical signs of Huntington’s disease

Answer 10

Clumsiness  
Agitation/irritability 
Anxiety 
Apathy 
Disinhibition - behaviour change 
Delusions and hallucinations 
Abnormal eye movement 
Depression

Question 11

What are the late clinical signs of Huntington’s

Answer 11

Dystonia 
Involuntary movement
Trouble with balance and walking
Lack of manual dexterity 
Slow voluntary movement and trouble initiating movement 
Speech and swallowing difficulty 
Choreiform movements 
Rigidity 
Dependence

Question 12

What causes Huntington’s

Answer 12

Mutations in the Huntington’s gene
Autosomal dominant
Mutated protein has too many glutamines which makes it neurotoxic

Question 13

Is there treatment for Huntington’s

Answer 13

No

Currently can only do predictive testing - tells people if they have it before symptoms

Question 14

What type of inheritance does spinal muscular atrophy have

Answer 14

Autosomal recessive

Question 15

What causes spinal muscular atrophy

Answer 15

Mutation that leads to lack of SMN1 protein

Progressive loss of anterior horn cells in spinal cord and brain stem nuclei - LMN loss

Question 16

What are the symptoms of spinal muscular atrophy

Answer 16

Hypotonia
Proximal muscle weakness
Tongue fasciculations
Respiratory failure in severe forms

Question 17

How can you treat spinal muscular atrophy

Answer 17

Give synthetic oligonucleotide to alter splicing and replace missing protein
Given via lumbar injection every few months

Question 18

When does Alzheimer’s usually occur

Answer 18

Old age

1/5 of the over 80s have it

Question 19

What causes Alzheimer’s disease

Answer 19

Can be inherited - mutations in APP, Presenilin 1 or 2
Can be spontaneous
Loss of cortical neurons
Extracellular protein deposits (plaques) containing amyloid B proteins
Neurofibrillary tangles

Question 20

What type of inheritance does Alzheimer’s follow

Answer 20

Autosomal dominant

Question 21

Which other genetic condition is Alzheimer’s associated with

Answer 21

Down’s syndrome

Amyloid gene is on 21 so they will produce more of the protein - more plaques

Question 22

Is there a genetic component to MS

Answer 22

It is probably polygenic - combined effects of many genes are predisposing to the condition
Doesn’t really run in families
Genes have minimal input