12 year-old Sadia Begum has become the first Royal Brompton patient to receive a diagnosis of her rare condition, Primary Ciliary Dyskinesia or PCD, via the 100,000 Genomes Project.
The project aims to sequence the genomes of 100,000 patients with rare diseases and common cancers, as well as their close relatives with the aim of allowing a better understanding of these illnesses and to help identify new and improved treatments for the future.
No-one has ever attempted whole genome sequencing of this scale before as part of everyday care in hospitals and so far over 22,000 genomes have been sequenced since December 2014. The full 100,000 genomes are projected to be completed by December 2018.
Sadia and her parents were recruited to the project at a routine clinic at the hospital and although she had been clinically diagnosed with PCD, the exact genetic cause, carrier status of her parents and risk to other family members, had not been clarified.
PCD is a condition characterised by lingering respiratory tract infections and patients may also have abnormally placed internal organs. Sadia was found to have a mutation in both copies of her DNAH5 gene which results in the cilia (the hair-like projections on the surface of cells) in her airways not being as flexible and motile as they should be. As a result there is an increased build-up of mucus in her lungs, making her more prone to infection.
The West London NHS Genomic Medicine Centre (GMC), which is led by Imperial Healthcare NHS Trust, and includes Royal Brompton & Harefield NHS Foundation Trust, Royal Marsden NHS Foundation Trust and Chelsea and Westminster Hospital NHS Foundation Trust, received Sadia’s results back from the project in December 2016. The result was subsequently validated and confirmed at Royal Brompton’s Clinical Genetics and Genomics Laboratory, one of three nominated validation laboratories for the GMC. PCD is one of the many inherited respiratory conditions for which the Clinical Genetics and Genomics Laboratory have recently developed a new “Respigene” gene panel.
The result was fed back to Sadia and her family and Rahima, Sadia’s mother, explained that it took many years before Sadia was given a diagnosis for her condition: “Immediately after Sadia was born she started to sneeze and had a lot of mucus coming out of her nose. Initially she couldn't feed properly because she was unable to breathe through her nose.
“She was referred to ear, nose and throat clinics from an early age and when she was three years old she had her adenoids and tonsils removed. It wasn’t until she was around five years old that doctors finally diagnosed her with PCD. There were mixed emotions. Initially it was a shock because we weren't expecting this kind of underlying illness.
“It was a relief that we knew what her illness was and then also upsetting because for five years no one knew what was wrong with her and at such a young age she had a number of procedures done which in hindsight maybe weren't necessary. Had she been diagnosed earlier then maybe her lungs would be in a better condition”
Dr Deborah Morris Rosendahl, validation and laboratory lead for the West London GMC, commented: “It’s very common for these very rare diseases to go undiagnosed for a long time and patients and their families suffer as a result. With this project the time it takes to sequence a whole human genome has been dramatically reduced and will allow for speedier diagnoses as part of routine care.”
The West London GMC is actively recruiting patients and their families to the project and has so far recruited over 1,000 participants. Patients who have not had a confirmed diagnosis of their rare genetic condition via routine genetic testing are eligible to have their genome sequenced and analysed.
For more details on referral and recruitment at Royal Brompton and Harefield hospitals, contact Geraldine Sloane, the Trust’s Project Manager for the 100,000 Genome Project, on 020 7352 8121 or by email.
For more information about the project, visit the Genomics England website