Week 5 - Duchenne Muscular Dystrophy

Question 1

What is the cause of muscular dystrophy?

Answer 1

• mutation in the gene producing dystrophin
• causes constant muscle contraction / relaxation
• weakens and destroys the muscle

Question 2

What are the types of muscular dystrophy?

Answer 2

becker
- not produce functional dystrophin
- limited function
- so less severe
duchenne
- not produce dystrophin
- no function
- more severe

Question 3

How can DMD be diagnosed?

Answer 3

blood Creatine PhosphoKinase (CPK) test
- damaged muscles can release kinase into blood
- elevated levels denote muscle injury
ElectroMyoGraphy (EMG)
- electrical signalling to and from muscle
- rules out neurodegenative diseases
muscle biopsy
- analysis of a sample of muscle tissue
genetic testing
- testing for mutations

Question 4

What is MLPA?

Answer 4

Multiplex Ligation-dependent Probe Amplification
- detects copy number changes
- can scan for intragenic deletions and duplications
- target sequence has pair of primers
- hybridise to sequences within target
- right probe contains stuffer fragment
- for variable lengths of PCR
- DNA ligase seals the two probes to create continuous sequence
- amplification
- separated by capillary gel electrophoresis
- half peaks suggests heterozygous deletion

Question 5

How does dystrophin work?

Answer 5

• forms structural link between actin filaments of cytoskeleton at N-terminal
• via membrane bound Dystrophin-Associated Protein (DAP) complex
• to ECM at C-terminal
• gives stability to sarcolemma
• contains spectrin-like repeats
• aid in shock absorbance from elastic recoil during contraction/ relxation
• not mechanically fragile muscle

Question 6

What is utrophin?

Answer 6

• forms Utrophin-Associated Protein Complex (UAPC)
• similiar to DAPCs
• lacks spectrin-like repeats 15 and 19
• only binds through N-terminal domain

Question 7

What is the principle of exon skipping?

Answer 7

• Antisense Oligonucleotides (AOs) used to mask exon (51) to be skipped
• to correct reading frame
• truncated but functional dytrophin
• milder symptoms

Question 8

Why can utrophin modulation treat DMD?

Answer 8

• switched off in maturing fibres when dystrophin is produced
• produced in early stages for repair after fibre damage
• independent of genetic fault
• can treat all DMD patients