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Chance meeting leads to breakthrough discovery of mutant gene

01 March 2021
Key Researchers
Laboratory Head
Dr Charlotte Slade (left) and patient Cynthia Agius never expected their chance meeting would lead to a research discovery.
Introduction

When WEHI clinician-researcher Dr Charlotte Slade crossed paths with patient Cynthia Agius, neither knew it would lead to a research breakthrough and a lasting friendship.

Charlotte

I met Cynthia 10 years ago when I was working as an immunology and allergy registrar at Royal Melbourne Hospital. I was struck by what an upbeat person she was, despite having to come into hospital regularly for intravenous antibody replacements. She was always friendly and grateful to the hospital staff for the care she received. Throughout everything, she has remained positive.

“I recruited Cynthia to our research study at WEHI in 2014. I was curious to find out why some patients with CVID developed more severe disease, while others did not.”
Dr Charlotte Slade

Cynthia has a condition called common variable immune deficiency, or CVID, a disorder that impairs the immune system. People with the condition are more susceptible to infection and can develop autoimmune and inflammatory diseases. Meeting Cynthia at the clinic, and others like her, made me want to learn more about what caused the condition.

I recruited Cynthia to our research study at WEHI in 2014. I was curious to find out why some patients with CVID developed more severe disease, while others did not. I had a strong suspicion Cynthia’s condition was genetic. Her mother also had CVID and, upon further investigation of her family history, we found that many of her mother’s relatives in the Netherlands also had the condition.

Through our research at WEHI, we discovered that Cynthia’s condition was caused by a mutation in the NFKB1 gene. Pinpointing the exact cause of her condition and being able to explain that to her family was rewarding. We screened her four children to see if they had inherited the mutated NFKB1 gene and learned that only one of her children, her daughter, had inherited the gene. Cynthia’s five-year-old granddaughter also had the mutated gene.

Working with Cynthia and her family has taught me a lot about the types of conditions gene mutations can cause. The information about the mutated NFKB1 gene and the ability to screen for it will help people to make better informed choices about their life, knowing that they have an increased risk of infection and other issues.

Having a relationship with Cynthia has spurred me on to find answers that might be beneficial for her treatment or for her children and grandchildren. When you have a personal relationship with your patients, you can’t help going that extra mile for them.

Cynthia

I was diagnosed with CVID 23 years ago. Not long afterwards, my mother was also diagnosed with the condition. We didn’t realise it at the time, but many of her 18 brothers and sisters in the Netherlands, and some of their children, also had the condition.

“Finding out that my CVID was caused by a genetic mutation was a relief in some ways. I am glad that my children were able to be screened for the mutation.”
Cynthia Agius

I’d had a lot of infections, but they were always put down to other things. I was getting sinus infections and chest infections and was in hospital three times a year with pneumonia. Nobody was able to pinpoint the cause of the infections. It was not until they realised my immunoglobulin (Ig) levels had dropped to zero that I was sent to see an immunologist and put on monthly infusions of antibody treatments.

“It was a breakthrough that Charlotte discovered the mutant gene in our family. Having this information can help patients and doctors make better informed decisions about treatments.”
Cynthia Agius

Charlotte was one of the registrars at the immunology clinic at Royal Melbourne Hospital where I had my monthly infusions. We bonded instantly.

A few years later, Charlotte asked me to be part of some research she was doing at WEHI. I was honoured to be involved.

Finding out that my CVID was caused by a genetic mutation was a relief in some ways. I am glad that my children were able to be screened for the genetic mutation. My daughter was diagnosed at a younger age than I was, so hopefully she will be better able to better manage her condition.

It was a breakthrough that Charlotte discovered the mutant gene in our family. Having this information can help patients and doctors make better informed decisions about treatments. I have gone through a lot with this condition, but I hope this makes things easier for other families like mine.

Charlotte is a beautiful, caring person. She is more than just a doctor; she has become a friend. We have a special bond that I think will last for many years to come.

Would you like to be involved in advancing medical research?

WEHI’s researchers are seeking members of the public who would like to contribute to better outcomes in the medical research sector through our Consumer Buddy program.

Consumer representatives do not need to have a science or medical background. Our researchers are interested in non-scientific perspectives to assist in communicating scientific information and relating laboratory research to community experiences.

Pairing consumers with researchers allows our scientists to make discoveries that improve human health. We are particularly interested in talking to members of the public who are current or past patients, family members, carers or friends of patients, with a desire to help improve research outcomes.

The disease areas we are most interested in finding consumer representatives for are: brain cancer, blood cancers (lymphoma, leukemia including AML, MML and CLL), lung cancer, bowel cancer, oesophageal cancer, melanoma, rare cancers, immunotherapy and cancer with an interest in CAR-T research, asthma and inflammatory bowel disease.

To learn more, contact Katya Gray on 03 9345 2981 or email consumers@wehi.edu.au.

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