Autosomal Muscular Dystrophies

Question 1

What is the inheritance pattern of Myotonic muscular dystrophy? (MMD or DM)

Answer 1

-autosomal dominanant

Question 2

What is the affected rate in DM?

Answer 2

1 in 8000

Question 3

What are the CK levels in a patient with DM?

Answer 3

Normal or slightly elevated

Question 4

What are the two different kind of DM?

Answer 4

DM1 and DM2

Question 5

What is the cause of DM1?

Answer 5

-trinucleoide repeat exansion of CTG (or GCT) in the gene DMPK

Question 6

Wat is the location of the DMPK gene?

Answer 6

Chromosome 19

Question 7

What is the normal number of CTG repeats in the DMPK gene and how many do affected individuals have?

Answer 7

• normal is between 5 and 35
• affected individuals have more than 50 and sometimes as many as 100-1000

Question 8

What repeat causes DM2?

Answer 8

CCTG repeat

Question 9

In what gene does the CCTG repeat that causes DM2 take place?

Answer 9

CNBR gene

Question 10

Is anticipation common in DM1?

Answer 10

Yes.

-the DMPK gene is unstable in suceptible to repeat expansion in subsewuent generations causing anticipation of severity and onset.

Question 11

What is the protein product of DM1? What is the suspected action?

Answer 11

DMPK thought to encode a protein kinase that is involved with calcium ion flux

Question 12

What does the DM2 gene encode?

Answer 12

-DM2 gene, CNBR or ZFN9, encodes a zinc finger protein.

Question 13

What are the diagnostic tools used for DM1 and DM2?

Answer 13

• PCR
• Southern blotting for larger repeats

Question 14

What is the main difference bewteen facioscapulohumeral dystrophy and other dystrophies?

Answer 14

-It affects the upper limbs whereas others do not.

Question 15

What is the inheritance pattern of facioscapulohumeral dystrophy?

Answer 15

Autosomal Dominant

Question 16

What is the range of CK levels for facioscapulohumoral dystrophy?

Answer 16

It can range from normal to 5 fold normal range

Question 17

What part of the body is affected by limb-girdle muscular dystrophies (LGMD)?

Answer 17

-both the arms and the legs (limb-girdle, duh)

Question 18

Are LGMD autosomal dominant or recessive? When is the onset?

Answer 18

Both.

• Recissive form: chidhood or teenage onset
• Dominant: adulthood onset

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Question 19

What protein is dysfunctional in LGMD?

Answer 19

genes encoding sarcoglycans.

Question 20

What is the inheritance pattern of Bethlem Myopathy?

Answer 20

Autosomal dominant

Question 21

What are the symptoms of Bethlem myopathy?

Answer 21

Proximal muscle weakness, and joint contractures.

Question 22

In bethlem myopathy, what chromosome contains a mutation? What substance does this result in malformation of?

Answer 22

-Chromosome 21

–>Type VI collagen

Question 23

What is the inheritance pattern of oculopharyngeal muscular dystropy (OPMD)?

Answer 23

usually autosomal dominant

Question 24

What is a distinguising feature of OPMD?

Answer 24

Late onset (40’s-50’s)

Question 25

What are the symptoms of OPMD? (think about it)

Answer 25

-drooping eyelids, facial and pharyneal weakness, may extend to limbs

Question 26

In what population is OPMD most common?

Answer 26

French canadians --\>occurs in Bukhran Jews of isreal and hispanics of nothern new mexico

Question 27

What mutation causes OPMD?

Answer 27

-Caused by a GCN repeat in the gene encoding poly-a binding protein (PABN1)

Question 28

Is anticipation observed in OPMD?

Answer 28

No

Question 29

What is malignant hyperthermia caused by?

Answer 29

-severe reaction to anaesthetics and depolarizing muscle relaxants that cause pathologic elevation of calcium ions

Question 30

what are the symptoms of MH?

Answer 30

-muscle rigidity, elevation of body temp, acidosis and tachycardia

Question 31

What is now used to treat MH and has lowered the deaths to about 10%?

Answer 31

Dantrolene

Question 32

What is the biochemical process that causes MH?

Answer 32

- Prolonged release of Ca by the defective pore stimulates myosin ATPase, which causes muscle rigidity. - Ca-ATPase pumps then wrk to pump Ca back into the SR and consume a large percentage of the ATP. - This stimulates glycogen catabolism and aerobic mitochondrial metabolism which results in production of ATP, CO2 and Heat.