Lecture 27: Muscular Dystrophy Flashcards

1
Q

Define muscular dystrophies.

A
  • Group of genetic disorders of muscle characterised by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement
  • Number of different types: Duchenne muscular dystrophy (DMD) => most severe and most common
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2
Q

Recall the symptoms of DMD.

A
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3
Q

Recall the causes of MD symptoms.

A
  • Increasing proximal limb muscle weakness due to progressive muscle degeneration
  • Caused by pathogenic variant in a gene encoding a muscle protein called dystrophin
  • Dystrophinfound in all muscle (located at sub sarcolemma) and brain
  • Forms link between actin (cytoskeletal) and extracellular matrix
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4
Q

Describe DAPC and mention its function.

A
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5
Q

Recall the effects of dystrophin deficiency/dysfunction.

A
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6
Q

Recall the consequences in DMD.

A
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7
Q

Compare Duchenne and Becker MD.

A
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8
Q

Recall the inheritance of MD.

A
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9
Q

Recall dystrophin gene and protein.

A
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10
Q

Duchenne mutations disrupt the reading frame and cause ______________________ –mRNA usually degraded. Becker mutations cause the reading frame to be intact resulting ___________________.

A

Duchenne mutations disrupt the reading frame and cause premature termination of protein and non-functioning protein –mRNA usually degraded. Becker mutations cause the reading frame to be intact resulting in a shorter but partially functional protein.

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11
Q

How are DMD and BMD diagnosed?

A
  • Creatine kinase(blood) –a screening test
    • Skeletal muscle isoform of creatine kinase levels are elevated in serum (20 to 50x)
    • Normal range: 40-240 U/L
  • Pathology of a muscle biopsy (‘gold’ standard –but now only done if DNA testing does not provide a result)
  • DNA tests – Tests look primarily for deletions (PCR, MLPA, chromosomal microarrays); sequencing (NGS) for other mutations
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12
Q

Recall histology and immunocytochemistry of DMD muscle.

A
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13
Q

Recall immunocytochemistry of BMD muscle.

A
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14
Q

Recall previous methods of DNA diagnosis of DMD/BMD.

A
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15
Q

Describe the role and limitations of MLPA in DMD/BMD diagnosis.

A
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16
Q

Describe the features of MLPA probes.

A
17
Q

Recall about DMD gene sequencing.

A
18
Q

Recall future therapies for MD.

A

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