Taking part in the 100,000 Genomes pilot project

Georgia, aged four, is under the care of Great Ormond Street Hospital (GOSH) clinical geneticists and attended GOSH to take part in the pilot study for the 100,000 Genomes Project. Here her mum, Amanda, tells us about taking part in a research study.

Living with an undiagnosed condition

“When Georgia was born by c-section in June 2011 we had 20 blissful, worry free minutes enjoying our first born child and then our world was shattered. The curtains were drawn round my bed and we were told that there may be a problem. A number of tests were carried out but all came back clear so we were discharged feeling apprehensive. 

“As a first time mum, I didn’t know what was normal but at around three months old I remember picking up another child the same age as Georgia and I just knew straight away from holding the baby that there was a difference between them and Georgia. The other child had started to gain strength and tone in their body while Georgia was very floppy.

“After that we quickly noticed that Georgia wasn’t meeting any of her milestones and by six months, she wasn’t flourishing and was very poorly with lots colds and sickness. At this stage our paediatrician suggested that her problems were likely to be in her genes. Basic genetic testing brought up nothing and so doctors explained that she was now in the realms of an undiagnosed genetic condition. I had no idea that it was possible to have an undiagnosed condition. I thought you get told you might have a genetic condition, you have the genetic test, and then you get the answer.

Photo credit: AHP photography
“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. We then found out about SWAN UK (Syndromes Without A Name) and discovered that around 7,000 children a year in the UK are born with a genetic condition that can’t be diagnosed. 

“Finding them was a real breakthrough moment and immediately it made life easier. Finding that other people are going through the same thing makes you feel that ‘if they can do this, we can too.’

“Between the ages of one and two, we discovered all the problems Georgia had one by one. As well as both physical and mental developmental delay, we found that she has a rare eye condition that affects her sight, her kidneys don’t function properly, and she has verbal dyspraxia and meaning we don’t know if she will ever talk.

“It’s very hard living with an undiagnosed child. It’s a constant rollercoaster of being tested for large numbers of horrific conditions before being given the all clear. 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. Basic hopes for health, growth and development are all uncertain and we don’t even know if she will have a normal life expectancy.

“When Georgia was two we enrolled on a study which looked at part of her DNA called the exome. It was thought that the exome carried all the most important information within it. But after two years of waiting, nothing significant had been found within Georgia that could explain her condition.”

100,000 Genomes Project

“We then heard about the 100,000 Genomes Project, which set out to have the most advanced and in-depth look at a person’s DNA by analysing the whole genome. As soon as I heard about the project, I wanted to get on it. I thought ‘if anything is going to get us an answer then we’ll try it.’

“We came to GOSH and met with Professor 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 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.

“I felt confident that they would find something one day but we didn’t know whether it would be in six months or 10 years. As we were one of the first families on the project, there were just no guarantees.

“It was almost exactly a year until we received a phone call from Maria. When she said that they’d found something it was one of the biggest days of my life. She explained that they had found a mutation in one half of a single gene in Georgia which was likely to be the cause of her problems. 

“Despite finding the mutation 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. 

“They will probably find many more children with the same condition now as when they see a child with neurological condition, they can check for this gene to start with.”

The future

“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 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% 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.”