The clinical and scientific researchers and practitioners in the TGMI are at the forefront of human genetics. Every month, one of them will be telling us why they are so committed to the vision of the TGMI, and sharing a bit more about their work and interests. This week we hear from Dr Sian Ellard. She is Consultant Clinical Scientist & Head of Molecular Genetics at the Royal Devon & Exeter NHS Foundation Trust, and Professor of Genomic Medicine at the University of Exeter
What has been the main focus of your work to date?
In 1995 I set up a new NHS Molecular Genetics Laboratory in Exeter to do both research and clinical testing. Working with Professor Andrew Hattersley on monogenic diabetes, we have discovered many novel disease genes and shown that patients with specific genetic subtypes can be treated more effectively with sulphonylurea tablets instead of insulin injections.
My laboratory provides an international clinical diagnostic service for monogenic diabetes and hyperinsulinism, as well as a range of services for patients with rare diseases or cancer. Most recently I developed an exome sequencing clinical testing service for paediatric disorders that has a diagnostic yield of >50%.
What are you most excited about in genetic medicine?
We now have the technology to provide a genetic test for most patients with a rare disease. Previously, genetic testing was only available for those patients with one of the more common rare diseases, where there was greatest demand (by test volume) for testing. This is because testing for each gene involved designing PCR primers one exon at a time, one gene at a time. With next generation sequencing we can now do a single test that detects disease-causing variants in most known disease genes. This technology has also hugely accelerated the pace of novel disease gene discovery. Over the next few years we hope to learn the underlying cause of nearly all of the rare diseases due to genetic causes. This will improve equity of access to genetic testing for patients with rare diseases.
What are you most concerned about in genetic medicine?
Missed opportunities for making correct diagnoses by not sharing variant data. The global genomic data exchange programme, Matchmaker Exchange, enables sharing of data held in different databases. My own experience of simply posting a gene name onto Gene Matcher has already led to the identification of two novel disease genes and an end to the diagnostic odyssey of 5 families. We have a wealth of data that could benefit patients in the UK and throughout the world. We also have excellent tools like the DECIPHER variant database, and we must quickly move to a position where global sharing of variants identified by clinical testing laboratories is a part of normal clinical practice.
Why did you get involved in TGMI?
To work with an amazing group of experts on a shared mission to maximise the benefits of genetics for clinical care.
What is the most important thing that you would like the TGMI to achieve?
Accessible information for healthcare staff and patients that will reduce misinterpretation of genetic variants.
If you had a magic wand (i.e. unlimited people/resources) what would you do to make genetic medicine work?
I would sort out an equitable funding mechanism for patients with rare diseases or cancer to benefit from the advances in genomic sequencing technology. Then I would fast-forward ten years to capture the data required for better interpretation of genetic variants and apply it now.
Do you have a favourite gene? If so – what and why?
It would have to be the ABCC8 gene which encodes the Sulphonylurea Receptor subunit 1 (SUR1). Together with the Kir6.2 pore-forming subunit it forms the pancreatic beta cell KATP channel. This acts as a switch that allows insulin to be released as blood glucose levels rise after a meal. In 1996 loss-of-function mutations were shown to cause congenital hyperinsulinism. Ten years later, our group discovered that gain-of-function mutations cause neonatal diabetes. We showed that these patients could achieve better blood glucose control by stopping insulin injections and transferring to sulphonylurea tablets.
As a clinical scientist, a highlight of my job is issuing results that mean a child will get a better quality of life and improved long-term prognosis by taking tablets rather than facing a lifetime of insulin therapy. From the scientific perspective, this gene is fascinating; a complex spectrum of dominant and recessive mutations that cause permanent or transient neonatal diabetes or hyperinsulinism.
What is a surprising fact that few people know about you?
In 2010 I climbed Kilimanjaro. It was an awesome experience and we raised over £7000 for FORCE, our local cancer support charity.
If you had a chance to experience a completely different career for a week, what job would you try?
I love being away from it all in snow-clad mountains, so I would like to try being a heli-ski guide for a week. I’d need that magic wand to improve my off-piste technique first!