Genetics Flashcards
1
Q
- Duchenne Muscular Dystrophy is what kind of disorder?
- Due to what kind of mutation in which gene?
A
MOST COMMON
- X-linked disorder
- Due to frameshift or nonsense mutations
- lead to truncated dystrophin protein (no functional protein)
- inhibited muscle regeneration
- lead to truncated dystrophin protein (no functional protein)
DMD is the largest protein coding human gene; increase risk of spontaneous mutations
2
Q
- What is the function of dystrophin ?
- Loss of dystrophin results in (like in Duchenne MS)?
A
-
Function:
- The Dystrophin protein provides a structural link between the muscle cytoskeleton and extracellular matrix to maintain muscle integrity.
Loss of dystrophin results in:
- myonecrosis
- increase creatine kinase and aldolase are seen
3
Q
How is diagnosis of Duchenne Muscular Dystrophy confirmed?
A
- Western blot
- muscle biopsy
4
Q
- What are some physical symptoms of Duchenne Muscular Dystrophy ?
- When does onset of symptoms appear?
A
- Onset before age of 5
-
Symptoms:
- Weakness begins in pelvic girlde muscles (wheelchair)
- progresses superiorly
-
Psudeohypertrophy of calf muscle
- due to fibrofatty replacement of muscle
-
Gower manuever
- use upper extremities to help stand up
- Waddling gait
- Weakness begins in pelvic girlde muscles (wheelchair)
5
Q
Histology of Duchenne Muscular Dystrophy?
A
Fibrofatty replacement of muscle
6
Q
- Becker MD is what kind of disorder?
- due to a mutation?
- Compare severity of Duchenne MD
A
- X linked disorder
-
Due to:
- non-frameshift mutation
- partially functional instead of truncated
- non-frameshift mutation
- Less severe than Duchenne
7
Q
- When do onset of symptoms begin in Becker MD?
- How is it diagnosed?
A
- Symptoms show up later; adolescent or early adulthood
- progressive disorder
-
Diagnosed when:
- patient shows pattern of weakness
- first problem in hips, thighs and shoulders
- Pseudohypertrophy
8
Q
- Difference between Becker and Duchenne MD?
- Variation between Becker?
A
-
Becker vs. Duchenne
- slower onset and progression
- except cardiac muscle
- slower onset and progression
-
Becker vs. Becker
- due to variation in site of mutation
9
Q
- Myotonic Dystrophy is the second most common?
- What aret he two types?
- Shows signs of?
A
- Second most common disorder
- Show signs of anticipation
- Type 1 and Type 2:
- Type 1 more common
- Both repeat expansion disorders
10
Q
- When do symptoms of Myotonic Dystrophy begin?
- What is seen?
A
- Symptoms begin in adults
- less severe
-
Show signs of:
- weakness with progressive muscle wasting
- prolonged muscular contractions
- can’t relax certain muscles
- speech may slur, jaw may lock
11
Q
- Compare Type 1 vs. Type 2 Myotonic Dystrophy:
- gene encoded
A
-
Type 1: (autosomal dominant)
- DMPK gene, protein kinase
-
CTG repeat
- more repeats = more severe = earlier onset (anticipation)
-
Type 2:
- CNBP gene, transcription factor
- CCTG repeat
12
Q
- What symptoms are seen in Myotonic Dystrophy Type 1?
- Due to mutation in?
- My Tonia, My Testicles, My Toupee, My Ticker
A
- CTG repeat expansion in DMPK gene
- abnormal expression of myotonin protein kinase
-
Symptoms:
- myotonia (inability to relax voluntary muscle)
- muscle wasting
- cataracts
- testicular atrophy (My Testicle)
- frontal balding (My Toupee)
- arrhythmia (My Ticker)
13
Q
- Pompe Disease (Type II) is due to which deficient enzyme?
- results in accumulation of?
- What is test is helpful in identifying?
A
-
Defect in:
- Lysosomal alpha 1,4 glucosidase (acid maltase)
- important in glycogen degradation
- Lysosomal alpha 1,4 glucosidase (acid maltase)
-
Results in:
- glycogen accumulates in lysosomes
- distorts myotubes and weakens muscles
-
Identify with:
-
Periodic acid-Schiff stain
- identifies glycogen
-
Periodic acid-Schiff stain
14
Q
- Symptoms of Pompe Disease?
- “Pompe trashes the pump”
- Onset?
A
- Progressive weakness
- respiratory muscles, hips, thighs, shoulders
- Cardiac problems
- Liver problems
Onset is infantile to adults
- earlier onset = faster progression
15
Q
- Charcot-Marie-Tooth disease are also known as?
- Group of progressive hereditary nerve disorders relatived to defective?
- Inheritance pattern?
A
- also known as hereditary motor and sensory neuropathy (HMSN)
- Due to:
- defective production of proteins involved in structure and function of peripheral nerves or myelin sheath
- all problems stem from lack of stimulation
- defective production of proteins involved in structure and function of peripheral nerves or myelin sheath
- Inheritance pattern:
- autosomal dominance
16
Q
- Charcot-Marie-Tooth disease (HMSN) is associated with what symptoms?
A
-
Associated with:
-
foot deformities (pes cavus)
- weak muscles opposed by strong ones distort normal position
- lower extremity weakness
- muscles atrophy due to lack of use
- sensory deficits
- dymelination of nerves leads to weakness, atrophy and chane in sensation
-
foot deformities (pes cavus)
19
Q
- When is onset/ what does it present with at first?
- What are later symptoms of Friedrich’s ataxia?
“Friedreich is Fratastic: he’s your favorite frat brother, always staggering and falling but has a sweet, big heart.
A
Loss of function of frataxin
-
Onset:
- in childhood with kyphoscoliosis
-
Findings: (starts slowly)
- Staggering gait
- Frequent falling
- pes cavus
- diabetes mellitus
- hypertrophic cardiomyopathy
21
Q
- Amyotrophic (no-muscle-nourishment) lateral sclerosis (ALS) is due to?
- results in?
- Sporatic vs. familial?
A
-
Due to:
-
progressive degeneration of upper and lower motor neurons (loss of cortical and spinal cord motor neurons)
- can be caused by defect in superoxide dismutase 1
-
progressive degeneration of upper and lower motor neurons (loss of cortical and spinal cord motor neurons)
-
Result in:
- atrophic and spastic paralysis
- asymmetric limb weakness
- bowel/bladder deficits
-
Onset:
- usually seen after 50 (sporatic)
- 10% have familial forms
22
Q
Differences between Becker, Duchenne and Limb Girdle Dystrophy:
- Inheritance
- Distribution
- Gene/Locus
- Key Concept
A
