B6-020 CBCL Muscular Dystrophy Flashcards
what cell serves to repair damaged skeletal muscle cells?
satellite cell
connective tissue that surrounds the entire muscle
epimysium
connective tissue surrounding a fasicle
perimysium
connective tissue surrounding an individual muscle fiber
endomysium
calcium is very high in the
sarcoplasmic reticulum
helps connect the dystroglycan complex to the cytoskeleton in the muscle
dystrophin
centrally placed nuclei in skeletal muscle
myopathy
satelite cells lie under the
ECM
lack of dystrophin leads to
tears in the membrane
severity of muscular dystrophy is related to how much […] is present
dystrophin
myoblast that does not fuse to form the myotube
satelite cell
inheritance pattern of Duchenne and Becker md
X linked recessive
progressive difficulty rising from floor or chair
Gower’s sign
**apparent by age 3
normal milestones until child begins to walk
duchenne/becker
cardiopathy is more often associated with [duchenne’s or becker’s]
Beckers
tent-shaped mouth
nasal speech
ptosis
frontal balding with temporal wasting
DM1
muscle weakness is initially distal limb, facial, and axial
can spread proximally later on
DM1
associated with heart block and sudden cardiac death
DM1
caused by loss of function mutation in DMD
Duchenne
caused by mutation in DMD leading to truncated protein
Becker
links the cytoskeleton to the ECM via dystroglycan
dystrophin
describe the pathogenesis of Duchenne
deletions/duplications cause frameshift in DMD gene -> diminished mRNA synthesis of DMD gene -> low/absent dystrophin
describe the pathogenesis of Becker
deletions/duplication maintain reading frame of DMD gene –> synthesis of truncated mRNA for dystrophin –> synthesis of a partially functional, shorter dystrophin protein
80% of female carries for DMD mutations show […] despite being asymptomatic
elevated CK
caused by toxic gain of mRNA function mutation
DM1/2
caused by mutation in DMPK gene
DM1
caused by mutation in CNBP
DM2
severity of DM1 disease process is correlated to
number of repeats in mutated gene
is thought to sequester splicing proteins leading to globally altered mRNA splicing
DM1/2
tandem repeat numbers increase with each generation
anticipation
examples of trinucleotide repeat disease [2]
huntingtons
DM1/2
are steroids used to treat Duchenne/Becker?
Duchenne- yes, been shown slightly beneficial in ambulatory stages
Becker- not recommended
what is the issue in treating MD with gene therapy?
the gene is too big for vector
**micro-dystrophin
how does micro-dystrophin work?
smaller version of DMD gene that maintains the essential part of protein
this can be used to “convert” Duchenne pathogenesis to Becker