From 6 million to 1 – Jessica’s story

Jessica and her family

Jessica and her family. Image courtesy of GOSH.

Jessica, aged 4, recently received a diagnosis of her rare condition. Her diagnosis means a treatment could be recommended too. She took part in the 100,000 Genomes Project, together with her parents, at Great Ormond Street Hospital, part of the North Thames NHS Genomic Medicine Centre. All three donated a small sample of blood and their genomes were sequenced.

Bioinfomaticians analysed Jessica’s genome sequence to find the cause of her condition. Our lead rare disease bioinformatician, Dr Katherine Smith, explains how.



To begin the analysis, every genome is compared to the reference human genome sequence we use as a guide. Jessica’s genome had 6.4 million differences, or variants, from the reference sequence. Because Jessica’s condition is rare, we knew that the variant we were looking for was rare too. So the next step in this case was to look for rare variants. Almost 700,000 were rare.

Using information from scientific studies and research papers, we then narrowed down the 700,000 variants to almost 3,000 that are predicted to cause a change in a gene product (a protein).

Jessica’s parents do not have the same condition – so the next stage was to look for differences between Jessica and her parents. Out those 3,000 variants, there were just 67 that were different between Jessica and her parents and could be the underlying cause of her condition.

Finding the right variant

We checked Jessica’s variants against a knowledge base curated by Genomics England – PanelApp. This tool has information on thousands of genes that may be linked to rare diseases, as reported by expert doctors and researchers. PanelApp is a crowdsourcing tool for the rare disease genetics community, and we are currently looking for more expert reviewers – please visit the PanelApp site for more information.

Out of the 67 variants, one was located in a gene listed in PanelApp as being linked to symptoms similar to Jessica’s. The name of this gene is SLC2A1.

Changes in the DNA sequence

The order of the letters (A,T,G,C) in your DNA, or genetic code, is important. They tell your body which amino acids, the building blocks for proteins, it should make.

When one of the letters in your DNA gets deleted, or if one gets added, it can change which amino acids are used to make a protein. This is called a frameshift mutation. The protein may not work properly, or it could not be made at all.

In Jessica’s genome, there is a deletion in one copy of her SLC2A1 gene. The deletion means that the protein can’t be made at all from that copy of the gene, so she doesn’t have enough in her body.

How does this explain Jessica’s symptoms?

The SLC2A1 gene makes a protein that transports a certain type of sugar into the brain. Two healthy copies of this gene are needed for this protein to transport enough of this sugar to fuel the brain. Mistakes in the SLC2A1 gene can cause ‘Glut1 deficiency syndrome’ – which is Jessica’s diagnosis.

Glut1 deficiency syndrome (opens in new window) affects only about 500 people worldwide.


Research has shown that in some patients who have Glut1 deficiency syndrome, a special low-carbohydrate diet can help reduce the number of seizures they experience. This ‘ketogenic diet’ provides an alternative energy source for the brain.

The ketogenic diet will be carefully tailored for any individual patient, and should only be used under the care of medical professionals.

It’s not always so straightforward

Jessica had a very positive outcome. For some families participating in the Project we won’t be able to clearly identify the cause of disease right away. For these families, we will ask experts in our research partnerships to continue looking for the cause. Even when a cause can be identified easily, this knowledge won’t always suggest an immediate treatment or come in time to change patient care.  However, identifying the cause can bring peace of mind, help unite families affected by similar genetic conditions, and inform family planning decisions.

Anyone who takes part in the Project will be helping others in the future with the same condition.

Support for rare disease patients

Listed here are several charities and support organisations. Each can provide information, support or services for families affected by rare diseases. They can help you share your story, connect with others, or get involved in research and awareness activities.

Contact A Family is a national charity for families with disabled children.

EURODIS, Rare Diseases Europe, is a patient-driven alliance of patient organisations representing 695 rare disease patient organisations in 63 countries.

Genetic Alliance UK is the national charity working to improve the lives of patients and families affected by all types of genetic conditions.

Rare disease UK is the national alliance for people with rare diseases and all who support them.

SWAN, Syndromes Without A Name UK offers support and information to parents of children with undiagnosed genetic conditions.

Unique, Understanding chromosome disorders aim to inform, support and alleviate the isolation of anyone affected by a rare chromosome disorder and to raise public awareness.

For support with a specific rare disease, you can search for patient organisations and charities on the Rare disease UK website.