Mutational Mechanism of Disease Flashcards
What are the causes (mutational) of disease
loss of function (most common)
gain of function
novel property
ectopic or heterchromic expression
Loss of function mutations
Single gene disorders almost always result from mutations that alter function of a protein
The majority of mutations will affect __________-
the function of a protein
Examples of loss of function
Duchenne muscular dystrophy
Hereditary neuropathy with liability to pressure palsies
Osteogenesis imperfecta
Alpha thalassemia
Turner
DMD
Chromosome
Xp21.2
DMD
Mutation?
Large deletion (multiple exons)
or
Nonsense (stop) mutation / frameshift –> premature termination
DMD
inheritance pattern?
X linked
DMD
Clinical
Boys with abnormal gain 3-5y/o
Calf pseudohypertrophy
Progressive involvement of respiratory muscles
DMD women?
Women may–>cardiomyopathy
DMD median death
18
Xp21.2
DMD
Hereditary neuropathy with liability to pressure palsies
Mutation?
Deletion of PMP22
PMP22 deleted in
HNPP mutation
PMP22 (HNPP) what is it’s function
integral membrane glycoprotein in nerves
HNPP (PMP22 deletion)
clinical
Repeated focal pressure neuropathies (carpal tunnel, peroneal palsy w/ foot drop)
First attack usually in 2nd-3rd decade
Recovery from acute neuropathy is often complete
Incomplete recovery –> mild disability
PMP22 deletion (HNPP) inheritance?
Autosomal dominant
PMP22 deletion (HNPP) most common cause
Unequal crossover between homologous repeats on 17p12
–> 3 copies PMP22 on one chromosome and 1 copy PMP22 on the other
PMP22 deletion –>
HNPP
PMP22 duplication –>
CMT1A
17P12 associated with
deletion - HNPP
duplication - CMT1A