Neurogenetics Flashcards
What mode of inheritance is Duchenne muscular dystrophy?
X-linked recessive
What mode of inheritance is Huntington’s disease?
Autosomal dominant
What mode of inheritance is Spinal muscular atrophy?
Autosomal recessive
What mode of inheritance is Alzheimer’s?
Polygenic or multifactorial
RARELY autosomal dominant
When is the onset of Duchenne’s muscular dystrophy?
Childhood
When is the onset of Huntington’s Disease most common?
30-50’s
How does Duchenne Muscular Dystrophy present?
Delay in motor development
Muscle weakness @ 3-4 y/o
- Gower’s sign (using arms to get up from knees)
- Toe walking
- Exaggerated lumbar lordosis
Calf hypertrophy
What gene has mutations in Duchenne muscular dystrophy?
Dystrophin gene
What does the dystrophin protein do?
Connects actin filaments, needed for muscle contraction
What are the two types of mutation in the select gene in Duchenne muscular dystrophy?
70% - Large scale deletion of dystrophin gene
30% - Point mutation, small insertion & deletion
How is Duchenne muscular dystrophy diagnosed?
- Raised CK (screening)
- Molecular genetic testing (diagnostic)
- Electromyography (EMG)
- Muscle biopsy (diagnostic) - not common
What is the inheritance pattern of limb girdle muscular dystrophies?
Autosomal recessive
Does Duchenne muscular dystrophy only effect men?
Yes
What is a common differential diagnosis for Duchenne muscular dystrophy?
Autosomal recessive limb girdle muscular dystrophy
How is Huntington’s characterized?
Involuntary movements that can effect limb, trunk and face
What cognitive effects can Huntington’s have?
Progressive dementia
- Progress to severe dependency and death over 15-20 yrs
What are some late signs of Huntington’s?
- Rigidity
- Bradykinesia
- Weight loss
- Inability to walk
- Trouble speaking & swallowing
- Behavioral changes
What physical changes can be observed in the brain of a Huntington’s patient?
Flattening of the lateral walls of the lateral ventricles
What genetic mutation causes Huntington’s?
Pathological expansion of CAG trinucleotide
What does the CAG trinucleotide code for?
Production of glutamine which is toxic to some cell types within brain
What gene is mutated in spinal muscular atrophy?
SMN-1
How does spinal muscular atrophy present?
Muscle weakness & wasting
- Proximal skeletal muscles
- Respiratory muscles
Due to loss of anterior horn cells and lower motor neurons
How can progression of spinal muscular atrophy be halted?
By binding a synthetic oligonucleotide containing exon 7 to the neighboring SMN2 gene
What is the underlying pathology of Alzheimer’s?
Loss of cortical neurons
AND
Abnormal deposition of proteins within and outside of cells
What are senile plaques in azlheimers?
extracellular protein deposits containing amyloid B protein
What genes are effected in the rare autosomal dominant form of Alzheimer’s?
APP gene
Presenilin 1 & 2
What does the ApoE4 gene do in relation to Alzheimer’s?
Predisposes to Alzheimer’s
