B6-020 CBCL Muscular Dystrophy

Question 1

what cell serves to repair damaged skeletal muscle cells?

Answer 1

satellite cell

Question 2

connective tissue that surrounds the entire muscle

Answer 2

epimysium

Question 3

connective tissue surrounding a fasicle

Answer 3

perimysium

Question 4

connective tissue surrounding an individual muscle fiber

Answer 4

endomysium

Question 5

calcium is very high in the

Answer 5

sarcoplasmic reticulum

Question 6

helps connect the dystroglycan complex to the cytoskeleton in the muscle

Answer 6

dystrophin

Question 7

centrally placed nuclei in skeletal muscle

Answer 7

myopathy

Question 8

satelite cells lie under the

Answer 8

ECM

Question 9

lack of dystrophin leads to

Answer 9

tears in the membrane

Question 10

severity of muscular dystrophy is related to how much […] is present

Answer 10

dystrophin

Question 11

myoblast that does not fuse to form the myotube

Answer 11

satelite cell

Question 12

inheritance pattern of Duchenne and Becker md

Answer 12

X linked recessive

Question 13

progressive difficulty rising from floor or chair

Answer 13

Gower’s sign

**apparent by age 3

Question 14

normal milestones until child begins to walk

Answer 14

duchenne/becker

Question 15

cardiopathy is more often associated with [duchenne’s or becker’s]

Answer 15

Beckers

Question 16

tent-shaped mouth
nasal speech
ptosis
frontal balding with temporal wasting

Answer 16

DM1

Question 17

muscle weakness is initially distal limb, facial, and axial
can spread proximally later on

Answer 17

DM1

Question 18

associated with heart block and sudden cardiac death

Answer 18

DM1

Question 19

caused by loss of function mutation in DMD

Answer 19

Duchenne

Question 20

caused by mutation in DMD leading to truncated protein

Answer 20

Becker

Question 21

links the cytoskeleton to the ECM via dystroglycan

Answer 21

dystrophin

Question 22

describe the pathogenesis of Duchenne

Answer 22

deletions/duplications cause frameshift in DMD gene -> diminished mRNA synthesis of DMD gene -> low/absent dystrophin

Question 23

describe the pathogenesis of Becker

Answer 23

deletions/duplication maintain reading frame of DMD gene –> synthesis of truncated mRNA for dystrophin –> synthesis of a partially functional, shorter dystrophin protein

Question 24

80% of female carries for DMD mutations show […] despite being asymptomatic

Answer 24

elevated CK

Question 25

caused by toxic gain of mRNA function mutation

Answer 25

DM1/2

Question 26

caused by mutation in DMPK gene

Answer 26

DM1

Question 27

caused by mutation in CNBP

Answer 27

DM2

Question 28

severity of DM1 disease process is correlated to

Answer 28

number of repeats in mutated gene

Question 29

is thought to sequester splicing proteins leading to globally altered mRNA splicing

Answer 29

DM1/2

Question 30

tandem repeat numbers increase with each generation

Answer 30

anticipation

Question 31

examples of trinucleotide repeat disease [2]

Answer 31

huntingtons DM1/2

Question 32

are steroids used to treat Duchenne/Becker?

Answer 32

Duchenne- yes, been shown slightly beneficial in ambulatory stages Becker- not recommended

Question 33

what is the issue in treating MD with gene therapy?

Answer 33

the gene is too big for vector **micro-dystrophin

Question 34

how does micro-dystrophin work?

Answer 34

smaller version of DMD gene that maintains the essential part of protein this can be used to "convert" Duchenne pathogenesis to Becker

Question 35

most commonly used RNA vector

Answer 35

lentivirus (HIV)

Question 36

most commonly used DNA vector

Answer 36

adenovirus

Question 37

how does antisense oligonucleotide therapy work?

Answer 37

ASO "masks" the splice site contained in the truncated mutation so that it is excised --> slightly shorter but functional mRNA

Question 38

RNA molecule that induces exon 51 skipping

Answer 38

eteplirsen

Question 39

which group in the eteplirsen trial showed the greatest decline in the 6MWT performance?

Answer 39

delayed treatment group after receiving the therapy

Question 40

premature stop codon therapy was first noted with

Answer 40

aminoglycoside antibiotics **kill the bacteria by inhibiting protein translation

Question 41

allows insertion of amino acids at PTC rather than termination **results in greater fidelity of ribosome at true stop codon**

Answer 41

PTC therapy

Question 42

MOA Translarna

Answer 42

PTC therapy **not approved in US due to low evidence

Question 43

small deletion that allows retains the open reading frame resulting in a partially functional protein

Answer 43

Becker

Question 44

deletion that shifts the reading frame and results in loss of dystrophin

Answer 44

Duchenne

Question 45

caused by repeat expansions in DMPK and CNBP genes

Answer 45

DM1/2

Question 46

why do mature skeletal muscle cells have multiple nuclei?

Answer 46

individual myoblasts align and fuse their membranes together

Question 47

myotonia can be demonstrated by striking the [...] with a reflex hammer

Answer 47

thenar eminence

Question 48

sharp adduction of thumb and firm contraction of thenar eminence upon percussion indicates

Answer 48

myotonia

Question 49

ASO therapy (eteplirsen) is designed to treat what type of mutation?

Answer 49

pre mature stop codon in exon 51

Question 50

perimysium surrounds the

Answer 50

fasicle

Question 51

endomysium surrounds

Answer 51

muscle fibers

Question 52

epimysium surrounds the

Answer 52

entire muscle

Question 53

myotonia is characteristic of

Answer 53

DM1/2

Question 54

cardiac conduction defects are more typically associated with

Answer 54

DM1/2

Question 55

MOA of micro-dystrophin

Answer 55

replacement of absent dystrophin

Question 56

what is the functional role of dystrophin?

Answer 56

links ECM through sarcolemma to cytoskeleton

Question 57

repeat expansions create mRNA with toxic GOF

Answer 57

DM1/2

Question 58

what is the inheritance pattern of myotonic dystrophy?

Answer 58

autosomal dominant

Question 59

histologic features of MD

Answer 59

variation of fiber size fiber necrosis fat/connective tissue proliferation increased internal nuclei no IHC staining for dystrophin

Question 60

inheritance pattern of trinucleotide repeat disorders

Answer 60

autosomal dominant

Question 61

in management of DMD, ensuring [...] is necessary to prevent osteoporosis

Answer 61

calcium intake

Question 62

do DM patients typically lose the ability to ambulate?

Answer 62

no

Question 63

skeletal muscle results from the fusion of thousands of

Answer 63

myoblasts

Question 64

[...] cell has multiple nuclei

Answer 64

skeletal muscle

Question 65

how does X inactivation effect muscle cells?

Answer 65

each cell is formed by many myoblasts that each have randomly assigned X inactivation, so the cell will have aspects of both X chromosomes

Question 66

what are some symptoms of neuromuscular disease in infants?

Answer 66

arthrogryposis hypotonia feeding difficulties respiratory problems

Question 67

what is the inheritance pattern of most GOF mutations?

Answer 67

autosomal dominant

Question 68

expected CK values of Becker/myotonic dystrophy

Answer 68

in the hundreds

Question 69

expected CK of Duchennes

Answer 69

in the thousands

Question 70

thumb abduction after percussion of the thenar eminence indicates

Answer 70

myotonia

Question 71

used to treat DMD patients with a premature stop codon in exon 51

Answer 71

eteplirsen

Question 72

can eteplirsen reverse the damage that has already occurred?

Answer 72

no, can help slow progression but does not reverse

Question 73

role of dystrophin

Answer 73

link cytoskeleton to ECM via distroglycan

Question 74

dystrophin binds [...] at its N terminal

Answer 74

actin

Question 75

dystrophin binds [...] at its C terminal

Answer 75

dystroglycan

Question 76

congenital DM1 is typically associated with a repeat length greater than

Answer 76

1000

Question 77

can Becker be differentiated from DMD on histology?

Answer 77

no

Question 78

GOF mutations are generally [inheritance pattern]

Answer 78

autosomal dominant

Question 79

are steroids an effective therapy for MD?

Answer 79

yes

Question 80

medication that decreases the rate of apoptosis of myotubes and decelerates myofiber necrosis in DMD

Answer 80

steroids

Question 81

used to treat heart failure that may arise in DMD

Answer 81

digoxin

Question 82

is exercise shown to be beneficial in the management of MD patients?

Answer 82

no, deteriorating muscles can not strengthen and can accelerate disease course

Question 83

centrally placed nuclei on histology indicates

Answer 83

muscle cell degeneration and regeneration

Question 84

base pair mutation that leads to a premature stop codon

Answer 84

nonsense

Question 85

the deletion maintains the reading frame

Answer 85

Beckers

Question 86

deletion disrupts the reading frame leading to loss of protein

Answer 86

Duchenne