StratifID – Stratifying Imprinting Disorders
Justin Davies, Gabriella Gazdagh, Deborah Mackay and Karen Temple
StratifID is the latest study by the Southampton Imprinting Research team and is funded by the Medical Research Council. The study aims to understand how a type of genetic change (multi-locus imprinting disturbance) affects growth, development and health in children with Silver-Russell Syndrome (SRS) and and other imprinting disorders.
We will stratify people with SRS, and other imprinting disorders, according to whether or not this genetic change is present and we will investigate the health consequences. This information will help medical teams to predict who will require specific interventions; medical therapy, nutrition, educational support etc, so we can optimise health in people with SRS over their lifetime. This could lead to a step change in personalised medicine for people with SRS.
Background
Our bodies are formed using the genetic ‘instruction book’ made of DNA, which we inherit from our parents. From our eyes to our toenails, every cell in our bodies contains the same DNA – but every cell uses it differently. DNA changes can cause genetic disorders that make people unwell from their birth. But some rare disorders aren’t caused by changes in DNA itself, but in how that DNA is used; these are called imprinting disorders.
SRS is an imprinting disorder that happens when DNA that should be used from only one parent’s instructions, is instead read from both parents’ copies, or neither. People with SRS have reduced growth both before and after birth, so they need a care plan that fits them and helps them to thrive.
But families and doctors know that one plan doesn’t fit all children with SRS; children vary in their growth, appetite, response to Growth Hormone, and many other ways, and we suspect that imprinting disturbances, more complex than currently recognised, underlie part of this variation.
What the team will do
We will recruit children with molecularly diagnosed SRS, and another imprinting disorder Beckwith-Wiedemann Syndrome. For each child we will create a detailed picture of their growth and development, and precisely map out the changes in how their DNA is used, and measure their metabolism using state-of-the-art tests (in a simple pee sample!). We will find patterns that link their imprinting disturbance with their clinical progress. If we stratify imprinting disturbances in this way, we can predict what management will be best for different people.
If you want to know more
The team behind this study would love to hear from families who have a child (ideally under ten years old) with molecularly diagnosed imprinting disturbances. The study will run for three years from September 2023. Most, but not all, children with molecular SRS will be eligible for the study. If you would like to learn more, please email [email protected] with the emailed subject ‘StratifID’.
