Session 5.3a - Lecture 2 - Introduction to Precision Medicine Flashcards
Fig. 2
Describe this pedigree
- Patient is IV.V
- Great-grandparents deceased (I.I & I.II)
- Grandparents deceased - Grandma (father’s mother) had dementia, passed away early 60s (II.I & II.II)
- Mother alive (III.IV)
- Father passed away age 59, diag. with AD age 55 (III.III)
- Father’s brother died early 70s of MI & pneumonia (III.II)
- Cousin no contact (IV.I)
- 3 brothers (IV.II, IV.III, IV.VII)
- Eldest brother died age 51 DOD 22/11/2009 (IV.II)
- Second brother well (IV.III)
- Youngest brother had CT brain scan confirmed appearances - AD (IV.VII)
- No longer married (line)
- In contact with daughter who is on anti-depressants (V.III)
Draw a pedigree of a male patient who has:
- 3 brothers: youngest had AD, eldest died but no AD
- 1 daughter
- father deceased with AD
- grandparents deceased: grandma had AD
See Fig. 2
Need to be able to draw a 3 generation pedigree
Fig. 2
A patient has come to you wanting genetic counselling on Alzheimer’s disease (AD). You can see his grandmother, father and youngest brother have all got AD.
Looking at the information, what suggests this is genetic?
- It’s in 3 generations
- Each member of the family who had Alzheimer’s received it before 65: Alzheimer normally appears after 65, before 65 is early-onset dementia which is familial.
At what age does dementia normally onset?
65
When does early-onset dementia start?
Before 65 years old
Dementia before 65 is called what?
Early-onset dementia, or young-onset dementia
What is one of the fundamental principles in clinical genetics in terms of testing?
We cannot offer testing to someone who has come to you for advice – have to first test and find a positive gene change in the person who’s affected
In clinical genetics you must first test and find a positive gene change in the person who’s affected, before the person you are evaluation. What problems can this present?
You have to get the patients’ consent – lot of legal issues, clin genetics is an ethical minefield
e. g. - if screening for dementia, who will give consent for someone who has dementia
- if patient doesn’t know they have the disease such as in dementia do they want to know etc.
Fig. 2
A patient has come to you wanting genetic counselling on Alzheimer’s disease (AD). You can see his grandmother, father and youngest brother have all got AD.
The panel was tested for dementia and came back negative - it was normal and there was no evidence of dementia.
Does this mean the patient will not have dementia?
Use the information in the pedigree to explain your answer.
If it wasn’t familial, then he has no further risk as compared to anyone else. However, we can see that his eldest brother died age 51 although he did NOT have dementia (white square). Thus, his family history needs to be investigated.
Fig. 2
A patient has come to you wanting genetic counselling on Alzheimer’s disease (AD). You can see his grandmother, father and youngest brother have all got AD.
The panel was tested for dementia and came back negative - it was normal and there was no evidence of dementia.
However, on further investigation, it was found that his eldest brother died from motor neurone disease.
Is motor neurone disease normally genetic?
In most cases it doesn’t run in families.
Fig. 2
A patient has come to you wanting genetic counselling on Alzheimer’s disease (AD). You can see his grandmother, father and youngest brother have all got AD.
The panel was tested for dementia and came back negative - it was normal and there was no evidence of dementia.
However, on further investigation, it was found that his eldest brother died from motor neurone disease.
Motor neurone disease is not normally genetic. Does this mean the patient is at no more risk of getting dementia? Use your knowledge of motor neurone disease and dementia.
In most cases, MND doesn’t run in families.
However, a particular type MND can be associated with early onset dementia - familial frontotemporal dementia.
What is motor neurone disease?
Motor neurone disease (MND) is a uncommon condition that affects the brain and nerves. It causes weakness that gets worse over time.
It’s always fatal and can significantly shorten life expectancy, but some people live with it for many years. There’s no cure, but there are treatments to help reduce the impact it has on your daily life.
What is the gene involved in familial frontotemporal dementia AND motor neurone disease?
C9ORF72 is linked to both FTD and motor neurone disease and some affected families have a history of both conditions.
Fig. 2
What is the most likely diagnosis for this gentleman?
Frontotemporal dementia
Fig. 2
Give the most likely diagnosis for this gentleman and explain why.
Frontotemporal dementia.
About 10-15 per cent of people with FTD have a very strong family history of the condition. This means having three or more relatives with FTD across at least two generations.
C9ORF72 is linked to both FTD and motor neurone disease and some affected families have a history of both conditions.
This patient has relatives who have died of early-onset dementia but also an elder brother who has died on MND - therefore, the family is likely to carry dementia associated with MND, which is familial frontotemporal dementia.
What is the gene involved in familial frontotemporal dementia associated with motor neurone disease?
C9ORF72
Name 5 things you need to consider when considering a genetic condition.
- FH
- Younger onset
- Which test?
- Heterogeneity
(Genetic/Phenotypic) - Research-?
Antisense
oligonucleotides
What is the most important thing you need to do when testing clinical genetics?
Take a good family history!
What is an important consideration of the diseases you are investigating in whether they are genetic?
If they have a younger onset
Why is what test you do important in clinical genetics?
Depending on which test you do - there is a big change in presentation – the same family, the same gene: e.g. test for dementia came back negative, but test for MND and realised there was a mutated gene.
What is important in heterogeneity in clinical genetics?
Understanding genes and their genetics and phenotypes, e.g. some diseases might present the same but have different genes, or some may have similar genes but different phenotypes - for example, MND and frontotemporal dementia are associated but might not get both, so different presentations.
What is antisense oligonucleotide treatment?
Antisense oligonucleotides (ASOs) are short, synthetic, single-stranded oligodeoxynucleotides that can alter RNA and reduce, restore, or modify protein expression through several distinct mechanisms
Why is it important specify exactly what disease someone has?
So you can find exactly the right treatment that will work for them - precision medicine
What is the 100,000 genome project?
UK is first country in the world to use DNA codes in mainstream medicine. So we are in threshold of revolution – genomic medicine is going to be introduced into the NHS
What is CRISPR technology or gene editing?
Precision medicine
https: //www.theguardian.com/science/2017/oct/25/chemical-surgery-can-correct-genetic-mutations-behind-many-diseases-study
https: //www.bbc.co.uk/news/uk-wales-40509516
https: //www.bbc.co.uk/news/health-41724994
https: //www.england.nhs.uk/wp-content/uploads/2016/09/improving-outcomes-personalised-medicine.pdf
What is clinical genetics?
‘Clinical Genetics is the medical specialty which
provides a diagnostic service and “genetic
counselling” for individuals or families with, or at risk
of, conditions which may have a genetic basis’
