Genetic tests aid rare disease treatment


Southampton is diagnosing and treating patients with immune disorders using the latest genetic techniques, paving the way for personalised treatments for those with rare diseases. 

Work in Southampton has seen several patients with rare immune disorders benefit immediately from collaborative research identifying changes in individuals’ genetic make-up, achieved through our NIHR Southampton Wellcome Trust Clinical Research Facility (NIHR WTCRF) and Wessex Investigational Sciences Hub (WISH) laboratory.

These cases give an insight into what could be possible on a larger scale in the future, as part of routine healthcare on the NHS, providing new hope for families affected by a rare disease.

Finding the genetic cause

Building on work by the WISH lab’s Clinical Exome Pilot study, Southampton researchers have identified the genetic cause of patients’ rare immune disorders, giving them a diagnosis that was not previously possible.

This involved using the WISH lab’s facilities to analyse all genes currently known to cause disease, with patients recruited through the NIHR WTCRF.    

In total, a dozen patients with immune disorders have received a diagnosis so far, enabling one patient to have their treatment modified and five to receive a new personalised treatment.

Personalising treatment

 Mathew’s parents first realised something was wrong when he was just a day old, when he reacted badly to his BCG vaccination. This was when they first found out he had an immune disorder.

Now ten years old, Mathew came to University Hospital Southampton due to another infection caused by bacteria similar to those in the BCG vaccine, this time in his hip.

He was treated by Dr William Rae, who has been awarded an NIHR clinical fellowship through the Translational Research Collaboration for Rare Disease to develop new personalised treatments.

To support their treatment, the family were asked if they would be happy to give blood samples, allowing their DNA to be analysed by the research team to find out if there was a genetic cause.

In just four weeks, they found a change in the INFGR1 gene that meant he had insufficient functional INFɣ, preventing his immune system from being able to fight off these infections.

He has now been prescribed regular injections of INFɣ, meaning his immune system can effectively fight off infections, preventing the need for major hip surgery and allowing him to have a normal life.

Changing lives

Similarly, two young children from another family are now taking folinic acid supplements that cure their anaemia and severe immune disorder, following research published in the Journal of Allergy and Clinical Immunology into the cause of their condition.

Researchers identified a change in the MTHFD1 gene that prevents their bodies from being able to convert folate (vitamin B9) from their diet into folinic acid, required for the production of blood cells and a fully functioning immune system.

This treatment means that these siblings will no longer be affected by the frequent infections that have dominated their young lives so far, and will be able to grow up to lead a normal life.

A glimpse of things to come

In the future, tests like this could become a routine part of healthcare, through initiatives like the 100,000 Genomes Project - a groundbreaking UK-wide programme to introduce genomics testing for patients with rare diseases and cancer into the NHS.  

The Wessex Genomic Medicine Centre and is currently looking for people with a rare disease or cancer to take part in the 100,000 Genomes Project. 

If you are interested in finding out more, please call 023 8120 6531 or email Ruth Challis at

Posted on Tuesday 13 December 2016