Mutations in single genes were found to cause previously undiagnosed conditions in two four-year-old girls, Georgia Walburn-Green and Jessica Wright, who are patients at Great Ormond Street Hospital (GOSH) in London.
Professor Lyn Chitty, a clinician at GOSH, said: 'It's really exciting to see the results coming through and the difference this can make for families. It increases confidence in the project and shows that the application of genomics can live up to the promise of changing the way we diagnose and treat patients in the future.'
Georgia has suffered from health problems since birth, including developmental delays, poor eyesight, kidney problems and verbal dyspraxia, meaning it's uncertain whether she'll ever talk. Her parents noticed that she was failing to meet normal developmental milestones, but doctors were unsure what was causing her condition, although they suspected a genetic origin.
Using whole-genome sequencing, scientists at GOSH identified a mutation in a gene called KDM5b. They then found the same gene change in two or three other children with similar neurological conditions, confirming that this was the mutation causing Georgia's symptoms.
It was also clear that her condition was not inherited from her parents but rather due to a spontaneous DNA mutation. If it had been an inherited condition, her parents could have had as high as a one in four chance of passing down the disease to any other children. Given this risk, they had held off from expanding their family, but they now plan to try for a second baby.
Jessica also had development delays and, from 13 months onwards, started to suffer from epileptic seizures. The mutation identified by the 100,000 Genomes Project (also a spontaneous mutation) has led to a diagnosis of GLUT1 Deficiency Syndrome, meaning that her brain doesn't receive enough energy to function properly.
Putting Jessica on a special high-fat (ketogenic) diet, could help her brain to get the energy it needs to manage her symptoms and improve her health.
Jessica's mother, Kate, said: 'More than anything, the outcome of the project has taken the uncertainty out for us and the worry of not knowing what was wrong. It has allowed us to feel like we can take control of things and make positive changes for Jessica. It may also open doors to other research projects that we can go on. These could be more specific to her condition, and we are hopeful that they could one day find a cure.'
The aim of the 100,000 Genomes Project, launched in 2014, is to provide diagnoses of rare diseases where previously there were none, as well as to enable new medical research and harness the potential of genomic data. The project also aims to sequence the genomes of cancer patients, to further understanding of the disease and guide doctors in providing personalised treatment.
NHS chief scientific officer Professor Sue Hill said: 'This is an excellent example of how whole-genome sequencing can finally provide the answers that families have been seeking out for years. These new insights set them free to make decisions about the treatment options for their child and how they move forward with future plans for their family.'