Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
56 Cards in this Set
- Front
- Back
|
What are some symptoms of Duchenne Muscular Dystrophy?
|
Waddling gait
Gower maneuver (difficulty getting up) early onset weakness death at about age |
|
|
What is Becker Muscular Dystrophy? what are some symptoms?
|
It is a variety of Duchenne MD
weakness in arms, muscular atrophy proximal muscles are weaker than distal muscles upper chest muscles = v. weak facial muscles fine |
|
|
Describe the inheritance of Duchenne Muscular Dystrophy.
|
Gene is carried on X chromosome.
So if mom is carrier, she has a 50% chance of giving it to kids. |
|
|
What is the difference between Becker and Duchenne Muscular Dystrophy?
|
Becker MD has later onset with less severe weakness
|
|
|
What is the female carrier phenotype for Becker/Duchenne MD?
|
Usually asymptomatic, but sometimes show signs of the disease
|
|
|
A patient with dystrophinopathy has elevated levels of what in blood?
|
creatine kinase (causes muscles to fall apart)
|
|
|
Becker MD and Duchenne MD both fall under what cateogry?
|
Dystrophinopathies
|
|
|
What causes dystrophinopathy?
|
Mutation on dystrophin gene
|
|
|
What is myoglobinuria?
|
Muscle breakdown, leading to myoglobin spilling out. Myoglobin in urine
|
|
|
What is the treatment for degenerating fibers in dystrophinopathy?
|
prednisone
|
|
|
What is the clinical spectrum of dystrophinopathies?
|
- Duchenne MD
- Becker MD - Manifesting females - Cardiomyopathy (inflammation of heart) - Myalgia, cramps - Myoglobinuria - creatine kinase elevation |
|
|
Where is the dystrophic gene located?
|
X chromosome
|
|
|
Describe the size of the dystrophin gene. what does it do?
|
Largest gene in humans
It's in small concentration in muscle, but has a critical function in muscle membrane function |
|
|
Where is dystrophin protein located?
|
Anchored to the sarcolemma membrane by a complex of proteins
|
|
|
What happens when you do dystrophin staining of a patient with DMD versus normal person?
|
Pt with muscular dystrophy: no staining
|
|
|
WHat are 2 reasons for heterogeneity of dystrophinopathies?
|
- Gene is very large
- Types of mutations differ |
|
|
What gene mutations cause Duchenne/Becker MD?
|
>60%: gene deletion
6% - partial duplication Rarer causes: continuous gene deletion Non-random X chromosome inactivation in females Turner syndrome X autosome translocation Mostly deletions (of exons 6-17) |
|
|
Discuss some causes of heterogeneity in DMD
|
1. lyonization
2. Different portions of gene have diff functions 3. Diff deletions produce diff clinical outcomes |
|
|
What are the two kinds of mutations that could occur in dystrophin proteins?
|
1. In-frame mutations - produce abnormal dystrophin protein
2. Out of frame mutations - produce truncated dystrophin protein |
|
|
Describe what kinds of dystrophinopathies different kinds of mutations can lead to.
|
Out of frame deletions (truncated protein): Duchenne MD
In frame deletions: N-terminus - severe Becker Proximal Rod - mild variant Distal Rod - typical becker C-terminus - Duchenne |
|
|
How do you diagnose a Duchenne MD patient? (2)
|
Dystrophin stain (on muscle biopsy)
White blood cell DNA to search for deletions |
|
|
What would the PCR look like for a patient w/ dystrophinopathy?
|
Not enough bands
|
|
|
Describe the inheritance of Fragile X syndrome.
|
X linked
|
|
|
Where is the mutation that causes Fragile X located?
|
Fragile part of the X chromosome (tail at the bottom of the X chromosome)
|
|
|
Name some physical clinical manifestations of Fragile X syndrome:
|
Mental retardation
Delayed development Long face, prominent jaw and forehead, large ears Strabismus (eyes dont line up in same direction when focusing) Large testes Hyperextensible joints Mitral valve prolapse Smooth skin |
|
|
Name some behavioral symptoms of Fragile X:
|
Hyperactivity
Decreased attention span Speech and language problems Autistic mannerisms Gaze aversion Hand flapping Hand biting Perseverative speech (repetitive) |
|
|
How is Fragile X transmitted (through mother/father/both)?
|
Female carriers can transmit it.
Some males can transmit the disease without having it. |
|
|
What is anticipation?
|
A tendency for worsening over successive generations.
- Seen in Fragile X |
|
|
What causes Fragile X?
|
CGG repeat expansion in FMR1 gene. larger the triplet repeats = + chance for clinical signs
|
|
|
What is it called if there's only 60-200 copies of the repeat?
|
premutation variant
|
|
|
When is expansion of triplet repeat most likely to occur?
|
If transmitted from females.
|
|
|
How does methylation of the DNA affect the repeats in Fragile X Syndrome?
|
+ methylation = + repeat size
+ methylation = decreased mRNA (b/c methylation inactivates the gene) |
|
|
What is the fragile X gene's function?
|
Transport/translation of dendritically localized mRNAs
May be involved in synaptic plasticity (learning, memory) |
|
|
What does having a premutation implicate?
|
Can transmit the disease, but not have it yourself.
|
|
|
Why are there different manifestations of Fragile X in males vs. females?
|
Because females are protected by the 1 normal X chromosome
|
|
|
What are the symptoms of Tuberous Sclerosis Complex?
|
Tumors of skin, brain, kidney, other organs
Developmental disorders Light-colored skin patches Seizures Autism |
|
|
What causes Tuberous Sclerosis Complex?
|
Mutations on 1 of 2 genes...Either TSC1 on chromosome 9, or TSC2 chromosome 16
Mutation is autosomal dominant - so 1 mutant copy of gene in cell |
|
|
What do TSC1 and TSC2 code for? What do these genes do?
|
TSC1 - hamartin
TSC2 - tuberin Regulate cell growth, also can act as tumor suppressors |
|
|
Is one mutant copy of TSC1/2 enough to confer Tuberous Sclerosis Complex?
|
NO, because the norrmal copy produces enough hamartin/tuberin to regulate cell cycle.
There needs to be a second mutation in the person's life to produce a tumor. |
|
|
Describe the brain pathology in Huntington's Disease.
|
Atrophy of caudate, putamen
|
|
|
What percentage of patients have onset in childhood?
|
10%
|
|
|
What is the inheritance of Huntington's Disease?
|
Autosomal dominant
|
|
|
What happens over successive generations of Huntington's Disease
|
Anticipation
age of onset decreases |
|
|
What causes HD?
|
Expansion of the CAG/polyglutamine tract on the HD gene on Chrom 4 (+ repeat lengths)
|
|
|
What does the HD gene code for?
|
Huntingtin - (function unknown)
|
|
|
Larger expansions of the CAG repeat occur when the disease is transmitted by the mom or dad?
|
Dad
|
|
|
What determines age of onset, severity of HD?
|
CAG repeat length
|
|
|
Do males or females exhibit greater increase in repeat length?
|
males
|
|
|
Why are babies' umbilical cords saved?
|
For adult stem cells
|
|
|
What kinds of things could adult stem cells treat?
|
leukemia
lymphoma hemoglobinopathies bone marrow failure syndromes congenital immunodeficiency syndromes inborn errors of metabolism |
|
|
How do you determine if a donor is suitable for stem cell transplantation?
|
If Human Leukocyte Antigen's are shared between individuals, they are a "match"
|
|
|
How many groups of HLA are?
|
HLA-A
HLA-B HLA-DR |
|
|
How is HLA inherited?
|
as 2 sets of 3 HLA groups (haplotype)
(each parent has 2 sets of 3 HLA groups) each haplotype (set of 3) is inherited as a unit |
|
|
What is the chance of inheriting all the same HLA types as your sibling?
|
25%
|
|
|
What is the chance for each possible HLA combination?
|
25%
|
|
|
If you have one sib, what's the chance of a perfect match?
2 sibs? 3 sibs? |
1 - 25%
2 - 44% 3 - 58% |
