First children receive a genetic diagnosis at GOSH as part of the 100,000 Genomes Project

The first children to receive a genetic diagnosis through the 100,000 Genomes Project have been given their results at Great Ormond Street Hospital (GOSH), part of the North Thames Genomic Medical Centre (NTGMC).

The results, which pinpoint changes in different single genes as the cause of two previously undiagnosed conditions, come from the first wave of families recruited to the project as part of the pilot phase of the project. These patients came from across the UK, some travelling long distances in order to take part in the rare genetic disease aspect of the pilot, which was led by GOSH.

Towards a better understanding of rare diseases

As well as removing a large amount of uncertainty for the families, the results stand to have a major impact on many areas of their lives including future treatment options, social support and family planning. They also have the potential to help many more children with undiagnosed conditions who may be tested for these genetic mutations early on and be offered a diagnosis to help manage their condition most effectively.

The 100,000 Genomes Project, launched in December 2014, set out to sequence 100,000 whole human genomes to help researchers and clinicians better understand, and ultimately treat, rare and inherited diseases and common cancers. The programme is now well established across the country with the NTGMC recruiting more than 100 families a month.

Living with an undiagnosed condition

Georgia is under the care of GOSH clinical geneticists and took part in the pilot study for the 100,000 Genomes Project. After a number of tests early on in Georgia’s life, paediatiricians concluded that Georgia had an undiagnosed condition.

“I had no idea that it was possible to have an undiagnosed condition,” said Georgia’s mum, Amanda. “I thought you get told you might have a genetic condition, you have the genetic test, and then you get the answer.

“Being told that Georgia had an undiagnosed condition was one of the hardest points of our lives as we felt like we were alone. We looked for support from various groups but without knowing Georgia’s condition there wasn’t anywhere we fitted in.”

The lack of a diagnosis for Georgia left her parents in an uncertain situation.

Amanda said, “It’s difficult to get support in the form of community nursing and schooling when you don’t fully know what’s wrong and you don’t know if your child is receiving the treatment they really need. Without a diagnosis, you also don’t have a prognosis so you don’t know what the future will hold for your child.”

After taking part in an earlier study, Georgia’s parents heard about the 100,000 Genomes Project and saw it as something that could potentially provide the answers they so desperately needed.

“I wanted to get on it. I thought ‘if anything is going to get us an answer then we’ll try it,” said Amanda.

“We came to GOSH and met with Maria Bitner-Glindzicz who talked us through the project. We were really keen and wanted to get signed up and on the pilot study straight away so we gave samples of all our blood on the same day.

“As soon as we were on the project, I felt a huge sense of relief. I felt that they now had all the information needed to look at the full picture and it just required someone to decipher and understand it. There’s nothing else we could do or give and there would be no other secrets to unlock with Georgia. They had her genome and so the answers had to be there somewhere.”

‘A mutation found’

Almost a year later, Georgia’s parents received a phone call from Maria, who explained that they had found a mutation in one of Georgia’s genes, which was likely to be the cause of her problems.

“When Maria said that they’d found something it was one of the biggest days of my life,” said Amanda.

“Maria explained that we all have genes that have been copied incorrectly and have mutations, but a lot of them are insignificant and don’t matter. They therefore had to cross check with other children with the same mutation to see if that particular gene change is likely to be causing problems. After finding two or so other children who had the same gene change and a similar neurological condition, doctors felt relatively confident that this gene was key to Georgia’s condition.

“The diagnosis is going to change quite a few things for us. We always thought we’d have another child but because it was unknown if this was an inherited condition, we were told that the chances of reoccurrence could be as high as 1 in 4. We held off expanding our family because of this but have now been told that we only have a 1 per cent chance of this happening again. The risk is still slightly higher than average so we have been offered a test bespoke to me that will check for that gene fault early on in pregnancy.

“As for Georgia, we are hoping that over time we will find out more about her condition and her prognosis. We also hope to connect with the other families that have children with the same gene change.

“It’s going to take time to find out more about this gene and what it controls and affects but I’m sure they’ll find more out. Medicine is not yet at the stage to offer genetic therapy but we have come so far in Georgia’s lifetime already that who knows what the future holds.”

Give to GOSH

Funds raised through the Give to GOSH appeal will fund research programmes to find new cures and treatments for children with rare diseases.

Donate here to ensure GOSH can continue to be a home away from home for sick children and their families; and house the skills and expertise that will help them to get better.