A streamlined method to find disease-causing single gene mutations has been developed to aid diagnosis of critically ill infants. A process that screens the entire genome takes as little as 50 hours and is intended for routine use by doctors without specialised training in genetics.
'By obtaining an interpreted genome in about two days, physicians can make practical use of diagnostic results to tailor treatments to individual infants and children', said Dr Stephen Kingsmore, director of the Center for Paediatric Genomic Medicine at Children's Mercy, USA who led the study.
Up to a third of neonatal intensive care patients have genetic diseases, which are highly variable and often hard to diagnose. There are few tests available for specific single-gene genetic disorders, and these often detect only the most common disease-causing mutations. Whole genome sequencing and analysis to diagnose a rare genetic disease may otherwise take several weeks and require the input of genetics experts. The time taken for test results is particularly important for neonatal intensive care patients, who often show very rapid disease progression after birth.
The team at Children's Mercy Hospitals and Clinics in Kansas City developed a new bioinformatics tool to aid rapid diagnosis of genetic congenital diseases, to be used with commercially available rapid whole genome sequencing. A doctor can list the patient's symptoms to narrow down the possible genes involved - for example, a type of epilepsy displayed by one of the patients in the study is likely to be linked to mutations in a set of 174 genes. After rapid whole genome sequencing from a blood sample, automated computer analysis focuses on finding changes in gene regions relevant to the patient's symptoms. The process costs £8,400 ($13,500) for every child tested.
For a minority of 70 genetic diseases, such as Krabbe disease, starting treatment as early as possible after birth can help prevent disabilities and life-threatening illnesses. However, many of the 3,500 currently described genetic diseases have no specific treatment.
'By shortening the time-to-diagnosis, we may markedly reduce the number of other tests performed and reduce delays to a diagnosis', said Dr Kingsmore. 'Reaching an accurate diagnosis quickly can help to shorten hospitalization and reduce costs and stress for families'.
Dr Elizabeth Worthey, an expert in genetics and genomics at the Medical College of Wisconsin in Milwaukee who was not involved in the study, told Nature News: 'All pretty big medical centres will be considering whether they can implement this within the next year'.
The study was published in the journal Science Translational Medicine.