Whole Genome Test Pinpoints Mutations in Neonates

There are at least 3,500 known genetic diseases caused by mutations in DNA, and treatments are available for more than 500 of them but currently it takes about a month to get the sort of results that allow pediatricians to make a definitive diagnosis.

Scientists at the Children's Mercy Hospital (Kansas City, MO, USA) used a whole genome sequencing (WGS) program they developed themselves called STAT-Seq, in conjunction with a sequencing machine, to cast a broad net over the 3,500 or so known genetic diseases and achieve results in time for doctors to make clinical decisions.

The prototype was tested by doing retrospective 50-hour WGS on two children whose molecular diagnoses had already been done the conventional way. Then the scientists did tests on children not tested before, and confirmed the results by sequencing genomes of parents and siblings. These tests revealed, in one newborn a severe Gap junction beta-2 protein (GJB2)-related skin disease. In another they uncovered Breast Cancer (BRCA1)-associated ataxia telangiectasia mutated (ATM) activator 1(BRAT1)-related lethal neonatal rigidity and multifocal seizure syndrome. They also found other gene defects in additional children, including a new disease-causing mutation, B-cell lymphoma 9-like protein (BCL9L).

The investigators have cut down the time by developing statistical software that matches up doctors' unique descriptions of the patient's condition and symptoms, against a comprehensive set of relevant diseases while looking at the genome test results. By allowing the individual features to be entered, the software substantially automates identification of the DNA variations that can explain the child's condition. The program they developed themselves, the STAT-Seq, was used in conjunction with a HiSeq 2500 sequencing machine (Illumina Inc., San Diego, CA, USA).

The authors concluded that rapid WGS can potentially broaden and foreshorten differential diagnosis, resulting in fewer empirical treatments and faster progression to genetic and prognostic counseling. By shortening the time-to-diagnosis, they may markedly reduce the number of other tests performed and reduce delays to a diagnosis, as reaching an accurate diagnosis quickly can help to shorten hospitalization and reduce costs and stress for families. The study was published on October 3, 2012, in the journal Science Translational Medicine.

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Children's Mercy Hospital
Illumina Inc.