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Improving the genetic diagnosis of rare childhood developmental disorders

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Thousands of babies are diagnosed with rare developmental disorders each year in the UK – usually, these are caused by particular changes (called mutations) in their genes.[1] These conditions can cause symptoms including learning difficulties, epilepsy, autism or heart defects. Despite genetic testing becoming more routine, it can be challenging to make a diagnosis when the impact of a specific mutation is unclear. Professor Matthew Hurles of Wellcome Sanger Institute and Dr Elizabeth Radford of the University of Cambridge are carrying out research that could help doctors to interpret the results of genetic tests more accurately. They are initially focusing on three severe developmental disorders, but their approach could ultimately lead to earlier diagnosis and improved treatment for children with a wide range of genetic conditions.

This project is jointly funded by Action Medical Research and LifeArc.

How are children’s lives affected now?

Our genes provide instructions on how to make proteins, the building blocks of cells. But any changes to our genetic makeup can alter how proteins are built and work.

“If a gene change causes an important protein to not work properly, this can have devastating consequences,” says Professor Hurles. “Research has so far identified 285 genes where changes can lead to rare childhood developmental disorders – and there are many more yet to be identified.2”

A child suspected of having a rare developmental disorder may be offered genetic testing to identify the cause of their condition. But it can sometimes be difficult for doctors to understand the significance of a gene change – whether they are harmless or affect the function of an important protein.

“A lack of a specific diagnosis can be distressing for families,” says Dr Radford. “It may also limit their opportunities to access support networks – and delay appropriate treatment for their child.”

How could this research help?

“We’re aiming to improve diagnosis of three rare childhood developmental disorders – GLUT1-deficiency syndrome, Barth syndrome and Renpenning syndrome,” says Dr Radford.

The researchers will use a cutting-edge technique to test the effect of thousands of changes in the genes that are known to cause these conditions – to find out which ones prevent proteins from working properly.

“We will generate a comprehensive summary, or map, of the impact of changes within these genes – which will help doctors to interpret whether a specific mutation is the likely cause of the condition,” says Dr Radford.

Identifying the significance of gene changes could help improve the diagnosis of these rare developmental disorders for children when they are young. This could help reduce uncertainty for families and enable earlier and potentially improved treatment – as well as provide access to genetic counselling.

“In 20 years, we anticipate that similar maps of genetic changes will exist for almost all rare genetic diseases caused by changes in a single gene,” says Professor Hurles.

This will have a transformative impact on people’s lives – providing answers for families and allowing them to plan better for the future.

Professor Hurles

Research table

Project details

Project Leader Professor Matthew E Hurles, PhD FMedSci FRS
Location Human Genetics, Wellcome Sanger Institute, Cambridge
Project Team Dr Elizabeth J Radford, BA MB BChir PhD MRCPCH
Other Locations Department of Paediatrics, University of Cambridge and Child Development Centre, Addenbrooke’s Hospital, Cambridge
Grant Awarded
Grant Amount £228,620
Start Date
End Date
Duration 36 months
Grant Code (GN number) GN2934


  1. Deciphering Developmental Disorders (DDD) study: [website accessed 01 November 2022]
  2. Kaplanis, J. et al. Evidence for 28 genetic disorders discovered by combining healthcare and research data. Nature 2020; 586: 757-762.


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