Genetics Flashcards
What type of inheritance is Duchenne muscular dystrophy
X linked recessive
Therefore more common in males
Describe the disease progression in DMD
Delay in motor development
Onset of weakness in pelvic and shoulder girdles age 3-4
Wheelchair bound by 10-12
Death by involvement of cardiac and respiratory muscles by 20s
What are the classic physical signs of DMD
Posture - hips forward
Hypertrophy of the calves
Gower’s sign - walk hands up legs to stand
Toe walking
What causes DMD
Due to fault in dystrophin protein - lack of it
Gene is on the X chromosome
This prevents muscle cells renewing themselves normally
How do you diagnose DMD
Clinical signs - developmental delay, toe walking, Gower's Raised CK Electromyography Muscle biopsy Molecular genetic tests
What is creatine kinase a test for
Non-specific for muscle disease
Leaks out of damaged muscle
When is the usual onset of Huntington’s disease
Between 30 and 50 years old
What type of inheritance does Huntington’s disease show
Autosomal dominant
Is Huntington’s a progressive disease?
YES
Progressive physical and cognitive symptoms
Will go on to become severely dependant and then die
What are the early clinical signs of Huntington’s disease
Clumsiness Agitation/irritability Anxiety Apathy Disinhibition - behaviour change Delusions and hallucinations Abnormal eye movement Depression
What are the late clinical signs of Huntington’s
Dystonia Involuntary movement Trouble with balance and walking Lack of manual dexterity Slow voluntary movement and trouble initiating movement Speech and swallowing difficulty Choreiform movements Rigidity Dependence
What causes Huntington’s
Mutations in the Huntington’s gene
Autosomal dominant
Mutated protein has too many glutamines which makes it neurotoxic
Is there treatment for Huntington’s
No
Currently can only do predictive testing - tells people if they have it before symptoms
What type of inheritance does spinal muscular atrophy have
Autosomal recessive
What causes spinal muscular atrophy
Mutation that leads to lack of SMN1 protein
Progressive loss of anterior horn cells in spinal cord and brain stem nuclei - LMN loss
What are the symptoms of spinal muscular atrophy
Hypotonia
Proximal muscle weakness
Tongue fasciculations
Respiratory failure in severe forms
How can you treat spinal muscular atrophy
Give synthetic oligonucleotide to alter splicing and replace missing protein
Given via lumbar injection every few months
When does Alzheimer’s usually occur
Old age
1/5 of the over 80s have it
What causes Alzheimer’s disease
Can be inherited - mutations in APP, Presenilin 1 or 2
Can be spontaneous
Loss of cortical neurons
Extracellular protein deposits (plaques) containing amyloid B proteins
Neurofibrillary tangles
What type of inheritance does Alzheimer’s follow
Autosomal dominant
Which other genetic condition is Alzheimer’s associated with
Down’s syndrome
Amyloid gene is on 21 so they will produce more of the protein - more plaques
Is there a genetic component to MS
It is probably polygenic - combined effects of many genes are predisposing to the condition
Doesn’t really run in families
Genes have minimal input
