Duchenne muscular dystrophy phenotype
- abnormal gait
- gower’s sign
- calf pseudohypertrophy
- mild intellectual disability
- cardiomyopathy
- 0 reproductive fitness
Duchenne muscular dystrophy
molecular defect
Dystrophin (DMD) gene mutation by:
- lg deletions or
- frameshifts
Normally, dystrophin links the cytoskeleton with the extracellular matrix.
Duchenne muscular dystrophy
mode of inheritance
X-linked recessive
Diagnosing Duchenne muscular dystrophy
Serum creatine kinase (w/o muscle biopsy)
Gower maneuver
How is Becker muscular dystrophy different from DMD?
BMD is due to smaller in-frame deletions
- more mild than DMD
- Still has high creatine kinase
- later-onset cardiomyopathy than DMD
Duchenne muscular dystrophy
treatment
Corticosteroids: prolong independent ambulation
many others
Role of manipulation of myostatin function in the treatment of muscular dystrophies
Myostatin is a growth regulator (inhibitor)
Regulates muscle mass by acting as negative feedback mech.
Possibly used to combat cardiomyopathy which makes heart (dilated, hypertrophic and restrictive)
Familial hypertrophic cardiac myopathy (FHC / familial HCM)
- mode of inheritance
- main mutation type?
AD
Mostly missense mut.
»> causes a mutation in cardiac myosin heavy chain where it interacts with actin and ATP
Familial hypertrophic cardiac myopathy (FHC / familial HCM) genetic characteristics
Shows:
- genetic heterogeneity: single phenotype caused by mult mutations
- incomplete Penetrance: they express disease it or they dont even though they have bad gene
Hypertrophic cardiac myopathy (HCM) phenotype
- Cardiomyocyte and cardiac hypertrophy.
- Myocyte disarray (compromised function.)
- Interstitial and replacement fibrosis (arrhythmia)
- Dysplastic arterioles (ischemia)
Malignant hyperthermia
- mode of inhertance
- mutation in which gene?
Dominant mode of inheritance
Mutation in RYR1 –> mut. RYR Ca2+ release channel in SR
What triggers malignant hyperthermia?
> > inhaling HALOTHANE or SUCCINYLCHOLINE anesthetics (like during breast surgery)
Describe physiological process that results in malignant hyperthermia
The anesthetics trigger inappropriate release of Ca2+
Meanwhile, Ca2+ still leaks out from SR
> > ATPase pumps Ca2+ back into SR in futile attempt.
–»heat is generated to lethal level (hyperthermia)
- tons of muscle simultaneously contracts
(muscle rigidity/muscle spasm) - Increase CO2 production
- Rhabdomyolysis
What is used to treat malignant hyperthermia?
what does it do?
Dantrolene:
blocks muscle contraction by blocking Ca2+ release from SR
Just for funsies, what is Pleiotropy? Phenotypic heterogeneity? Allelic heterogeneity?
Pleiotropy: (disco ball) single gene mutation –> mult. Phenotypes
Phenotypic heterogeneity: mut in same gene –> diff phenotype
Allelic heterogeneity: mult mut in same gene –> similar phenotype
(Very similar/same as genetic heterogeneity (not sure)
