The clinical and scientific researchers and practitioners in the TGMI are at the forefront of human genetics. Every month, one of them will 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 Helen Firth, Consultant Clinical Geneticist at Cambridge University Hospitals Trust.
What has been the main focus of your work to date?
Using new genomic technologies for diagnosis and discovery in rare disease. Although individually rare, rare diseases are collectively common and affect ~1 in 17 people during their lifetime. Most rare disease is genetic in origin and this is especially true for rare disorders with early onset (prenatal, infancy, childhood). I am Clinical Lead for DECIPHER, a global data-sharing and interpretation platform to map the clinical genome, and for the Deciphering Developmental Disorders study (the DDD study ) a UK wide-project that is pioneering the use of genome-wide sequencing in rare disease diagnosis, generating whole exome sequence data on >30,000 people.
What are you most excited about in genetic medicine?
The potential to improve diagnosis for patients with rare disease and to identify new genes for rare disease. As an example, the DDD study has already identified more than 30 new genes for developmental disorders, enabling more individuals to be given a diagnosis and enabling rational approaches to therapy to be considered.
What are you most concerned about in genetic medicine?
The potential for overdiagnosis. We all have ~4.1 million genomic variants in our genomes; identifying which variants are disease-causing is a very challenging task (rather like looking for a ‘needle in a haystack’). It is seductively easy to persuade yourself that a variant in a given gene might in some way be linked to the clinical features in a patient – this phenomenon has been termed the ‘narrative potential‘ of a genome. An error in genetic diagnosis for an individual can be compounded by offering genetic testing to their relatives, thus amplifying the original error manyfold and potentially causing harm to many members of a family.
Why did you get involved in the TGMI?
To work with a group of talented and committed colleagues to drive forward the responsible and skillful implementation of genomic medicine; maximising the undoubted benefits and minimising the potential harms.
What is the most important thing that you would like the TGMI to achieve?
The safe, responsible and evidence-based implementation of genomic medicine supported by a coordinated infrastructure that enables clinicians and patients to understand the relevance and significance of genomic findings for health.
If you had a magic wand (i.e. unlimited resources) what would you do to make genetic medicine work?My ambition would be that every person with a rare genetic disease has the opportunity for diagnosis using a genome-wide technology and every person with a new diagnosis of cancer has the opportunity for the molecular signature of their cancer to be analysed using a cancer panel. This approach wouldn’t require a magic wand, as using WES (whole exome sequencing) and a cancer panel could be affordable and deliverable in the UK today. This application of genomic technology would truly transform diagnosis and management for patients on a large scale.
Do you have a favourite gene? If so – what and why?
I would choose the gene SATB2, as in 2003 I had the opportunity to work with Prof David FitzPatrick (also a member of TGMI) to identify this gene as a cause of cleft palate. I have had the great pleasure of working with David on the DDD study since 2010 and SATB2 has turned out to be one of the most frequent diagnoses amongst the myriad of rare developmental disorders that we have diagnosed in this study.
What is a surprising fact that few people know about you?
I took up running a couple of years ago and have now run further than the distance from Land’s End to John O’Groats in 5km chunks.
If you had a chance to experience a completely different career for a week, what job would you try?
I very much enjoy my work as a Consultant Clinical Geneticist so I haven’t given this a lot of thought, but it would be fun to try being an orchestral conductor for a week, rehearsing and performing a work like Haydn’s Creation.