Flashcards in Lecture 34 - Other MD's Deck (29):
What are the factors of classification of MD's?
Age of onset
pattern of weakness
pattern of inheritance
involvement of other systems
Specific abnormalities on muscle biopsy
causative gene where identified
What other systems can be involved in MD's?
Musculoskeletal (spinal rigidity, scoliosis, joint contractures)
After a muscle biopsy, what is done with the muscle?
stain with fluorescent antibody staining for membrane proteins
Myotonic dystrophy is the most common in __
Myotonic dystrophy is _______ ______t inhertance
Myotonic dystrophy is a multisystem disorder affecting:
proximal and distal weakness and wasting
smooth muscle (constipations)
Myotonic dystrophy has 3 phenotypes, what are they?
congenital - most severe, resp.failure
classic - most common, muscle weakness presenting in adolescence
mild - cataract and
Congenital Myotonic dystrophy babies will usually die in the first 4 weeks of life. If they survive, the babies will be
Myotonia is a characteristic found in some muscular dystrophies, what is it?
delayed relaxation of muscles after contraction
more often when cold and exercising
True or False
There are Increased central nuclei in Myotonic dystrophy
Mutant RNA transcribed from the expanded allele induce symptoms of the disease
RNA CUG expansions fold into hairpin like secondary structures which sequester specific proteins, resulting in....
depletion below a functional threshold
Two important proteins bind to CUG repeats: MBNL1 and CCUGBP1
In Myotonic dystrophy, ____ is sequestered on CUG repeat-containing RNA, resulting in loss-of-function
In Myotonic dystrophy, MBNL1 is sequestered on CUG repeat-containing RNA, resulting in loss-of-function
CUGBP1 is __-______, causing downstream effects such as disrupted regulation of alternative splicing, mRNA translation and mRNA stability
CUGBP1 is up-regulated, causing downstream effects such as disrupted regulation of alternative splicing, mRNA translation and mRNA stability
Embryonic stage; MBNL1 nuclear levels ___, CUGBP1 levels ___
Embryonic stage; MBNL1 nuclear levels low, CUGBP1 levels high
During development MBNL1 nuclear levels _____while CUGBP1 levels ______, inducing and embryonic-to-adult transition of downstream splicing targets
During development MBNL1 nuclear levels increases while CUGBP1 levels decrease, inducing and embryonic-to-adult transition of downstream splicing targets
Limb-girdle muscular dsytrophies are generally ____muscle disorders
Limb-girdle muscular dsytrophies are generally progressive muscle disorders
Limb-girdle muscular dsytrophies (LGMD) equally occur in
males and females 2-6th decade
Is there CNS involvement with Limb-girdle muscular dystrophies?
What are the tyopes of inheritance for Limb-girdle muscular dsytrophies?
AR - LGMD type 2 (much more common)
AD - LGMD, type 1
What are the clinical clues to Limb-girdle muscular dsytrophies?
creatine kinase levels
- genetic testing, blood samples
Limb-girdle muscular dsytrophies are associated with ____ viewable in histology
as well as Myotillin aggregates
Presentation of FSHD?
facial weakness - sleep with their eyes open
proximal arm weakness
what is the selective muscle involvement in FSHD?
Weakness often pathy/asymmetrical
scapula and pectoral muscles affected early
lower 1/3 of abdomen - Beevor sign
heart/respiratory usually unaffected
Is the gene for FSHD known?
The penetrance is incomplete, so ..
30% all inherited cases are asymptomatic - symptoms more common in males
FSHD can be linked to a deletion of ___ repeat sequence on chromosome 4
most people have 12-96 copies
FSHD patients, no more than 8
The smaller the fragment of D4Z4 ...
the more severe the FSHD - will onset earlier
The problem with gene detaction for D4Z4 is that...
the gene probe detects changes in homologous areas on chromosome 4 & 10