Professor Grant Stewart is studying cells from children with skeletal disorders to understand how genetic differences between patients affect the symptoms and severity of their condition. This could help to uncover new ways of treating the conditions, as well as identifying children at greater risk of developing cancer due to the genetic mistake.
Why this research is vital
‘Skeletal dysplasia’ describes a large group of conditions that cause deformities of the skeleton and/or cartilage in children. Each year these conditions affect around 1 in every 5,000 births worldwide and are usually associated with other symptoms.
Children living with skeletal dysplasia may have difficulties with movement caused by abnormally shaped bones, and various other severe symptoms such as difficulties breathing, fluid build-up on the brain, and chronic pain.
Researchers have identified more than 360 genetic faults linked to skeletal dysplasia, some of which are also known to increase the risk of a child developing cancer.
But for many children, their condition has not yet been linked to a specific genetic cause. That makes it very difficult to offer treatment or let families know how the disease is likely to progress in future. This can leave children living with debilitating symptoms and an uncertain future.
Professor Grant Stewart and his team have recently identified a particular genetic mistake linked to various forms of skeletal dysplasia. The genetic fault – known as TONSL – occurs in children with a wide range of symptoms and severity of disease, from short stature and immune system problems, to disorders causing extreme dwarfism and a small head and brain. The team believe this genetic fault could play a central role in causing a particular group of skeletal dysplasias.
The team hopes to discover why certain groups of children with skeletal dysplasia display such different symptoms and severity of disease, even with a mistake in the same gene.
They will look at the role a genetic fault (TONSL) plays in causing these variations. They will study cells taken from patients who carry the TONSL fault in their DNA, carrying out tests to determine the precise effect that genetic fault has on various processes in the body.
Impact of this project
Understanding the causes of skeletal dysplasia and why some children have more severe symptoms than others could help researchers find new ways of treating the conditions. This could offer children hope of avoiding the various debilitating symptoms.
Genetic mutations can also increase a child’s risk of developing cancer in the future, so the team’s work could help to identify those most at risk and take steps to treat or support the child and their family.
This project is jointly funded by Sparks and charity partner Great Ormond Street Hospital Children’s Charity through their national research funding call.