Kevin Mitchell Rare Disease Day 2016 Presentation
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Transcript of Kevin Mitchell Rare Disease Day 2016 Presentation
![Page 1: Kevin Mitchell Rare Disease Day 2016 Presentation](https://reader033.fdocuments.us/reader033/viewer/2022051707/58edf7881a28aba71c8b4693/html5/thumbnails/1.jpg)
Are common
disorders really
collections of rare
disorders?
Kevin Mitchell
Institute of Genetics
Trinity College Dublin
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Common vs Rare
Autism
Epilepsy
Schizophrenia
IntellectualDisability
VCFS (22q11)
Fragile XRett
Pitt-Hopkins
TimothyWilliams
Tuberous sclerosis
Angelman
Prader-Willi
![Page 3: Kevin Mitchell Rare Disease Day 2016 Presentation](https://reader033.fdocuments.us/reader033/viewer/2022051707/58edf7881a28aba71c8b4693/html5/thumbnails/3.jpg)
Diagnoses of exclusion
• Major diagnostic categories are based on
similarity of symptoms and ignorance of
causes
• Psychological symptoms are defined by
interview/behavioural reports – no blood
tests, brain scans, or other biomarkers
• Underlying mechanisms may be highly
diverse
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Genetics reveals diversity of causes
• Traditional cytogenetics
• Molecular technologies to detect
chromosomal deletions and duplications
• Genome sequencing to detect single
mutations
More and more cases of “common disorders”
recognised as discrete, rare genetic conditions
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Traditional cytogenetics
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Can reveal large differences
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Comparative genomic hybridisation
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CGH allows detection of even small events
and gives precise molecular information
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Can identify which genes disrupted
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Whole-genome sequencing
…CCTAAACTTTG…
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Genetic variation
• Each of us carries ~150 mutations affecting
different proteins
• Sometimes one or more of those mutations
cause disease
![Page 15: Kevin Mitchell Rare Disease Day 2016 Presentation](https://reader033.fdocuments.us/reader033/viewer/2022051707/58edf7881a28aba71c8b4693/html5/thumbnails/15.jpg)
How many cases can be diagnosed?
(2011)
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Complexity of genetic effects
• Some cases may have one identifiable genetic cause
• Many others may involve multiple genetic effects
- probably a unique spectrum in each person
• Specific mutations can have diverse effects across
people
![Page 19: Kevin Mitchell Rare Disease Day 2016 Presentation](https://reader033.fdocuments.us/reader033/viewer/2022051707/58edf7881a28aba71c8b4693/html5/thumbnails/19.jpg)
Why make genetic diagnoses?
• Diagnostic certainty
• Information on whether mutations are inherited or new
• Prediction of risk to subsequent children
• Therapeutic implications in some cases
• Driving rare disease research
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Conclusions
• Common diagnostic categories hide underlying
genetic diversity of causes
• Rare disorders may be collectively much more
common than currently recognised
• Genetics is revealing many underlying causes
• Genetics services need to keep pace with rapid
advances in science