Genetics of Neuropsychiatric Diseases Flashcards
What is pleiotropy?
Pleiotropy is the phenomenon in which one gene influences two or more seemingly unrelated phenotypic traits.
What inheritance pattern does Huntington’s disease show?
List the symptoms of Huntington’s disease.
What causes these symptoms?
- Huntington’s shows an autosomal dominant inheritance pattern.
Early symptoms of Huntington’s:
1 - Slight uncontrollable muscle movements.
2 - Clumsiness.
3 - Lack of concentration.
4 - Changes of mood.
Late symptoms of Huntington’s:
1 - Aphasia.
2 - Dysphagia.
3 - Worsened clumsiness.
4 - Cognitive impairment (loss of drive, initiative and organisational skills).
5 - More severe changes of mood.
- Symptoms of Huntington’s disease arise from neuronal death in the striatum (movement) and frontal lobe and limbic system (cognition).
- See A* card 36 for details on pathophysiology and novel treatment.
What feature of the Huntington gene determines disease severity and age of onset?
- Number of CAG repeats determines disease severity and age of onset in Huntington’s disease.
- Up to 36 CAG repeats is expected in healthy individuals, but in patients with huntington’s disease, there can be 36-121 CAG repeats.
What is frontotemporal dementia?
What are the symptoms of frontotemporal dementia?
- Frontotemporal dementia is a group of diseases similar to Huntington’s but without the movement deficits.
- It is the second most common cause of dementia in people under the age of 65.
Symptoms include:
1 - Behavioural changes.
2 - Cognitive disturbance.
3 - Aphasia.
*Motor disturbances can sometimes be present, in which case the disease is named e.g. ‘frontotemporal dementia with Parkinson’s disease’.
What is Pick’s disease?
What causes Pick’s disease?
- Pick’s disease is a type of frontotemporal dementia.
- It is characterised by Pick bodies (inclusions composed of tau proteins) in the frontal lobe and dentate gyrus in the hippocampus.
- Pick’s disease occurs due to null (silencing) mutations in the progranulin gene, a gene linked closely to the tau protein.
- Progranulin is involved in:
1 - Development.
2 - Wound repair.
3 - Inflammation.
4 - Activation of microglia in neurodegenerative disease.
What inheritance pattern does Alzheimer’s show?
List the genes involved in Alzheimer’s.
How can Alzheimer’s be characterised histologically?
List the symptoms of Alzheimer’s.
- Typical Alzheimer’s disease shows a complex, non-Mendelian inheritance pattern.
- Early onset Alzheimer’s shows an autosomal dominant inheritance pattern.
- Genetic risk factors for Alzheimer’s include amyloid precursor protein, presenilin-1, presenilin-2 and ApoE (esp. ApoE4 polymorphism).
- Histologically, it is characterised by the presence of amyloid plaques.
Symptoms include:
1 - Memory loss (primary symptom).
2 - Aphasia.
3 - Dysphagia.
4 - Depression.
5 - Hallucinations.
6 - Cognitive impairment.
List the Mendelian inheritance patterns.
Mendelian inheritance patterns include:
1 - Autosomal dominant.
2 - Autosomal recessive.
3 - X-linked dominant.
4 - X-linked recessive.
5 - Mitochondrial.
List 3 effects of ApoE4 genotype on Alzheimer’s disease progression.
ApoE4 affects Alzheimer’s by causing:
1 - Earlier, more fulminant onset.
2 - Increased amyloid load in the brain.
3 - Increasing Alzheimer’s progression due to head injury.
What inheritance pattern does bipolar disorder show?
List the regions of the brain affected in bipolar disorder.
- Bipolar disorder a complex, non-Mendelian inheritance pattern, involving hundreds of genes.
Bipolar disorder affects the:
1 - Prefrontal cortex.
2 - Limbic areas.
