Image: The HiSeq 2000 sequencing system (Photo courtesy of Illumina).
A new genetic sequencing test moves beyond assaying for one disease at a time, making it possible to identify more than 750 diseases triggered by mutations in children concomitantly and deliver results within six to eight weeks.
Currently, most genetic tests for childhood diseases are conducted one at a time, and this trial-and-error process consumes valuable time for clinicians in the search for the most effective treatment options for their patients and for families and the healthcare system, the prolonged hunt means higher costs.
Scientists at Children's Mercy Hospital (Kansas City, MO, USA) developed a screening panel, called the Targeted Gene Sequencing and Custom Analysis (TaGSCAN) that covers the 514 genetic regions that code for pediatric conditions with possible hereditary or elusive diagnoses. TaGSCAN is a hybrid of hypothesis-based and non-hypothesis-based testing. In a study involving 107 patients with neurodevelopmental disorders, 40 of these patients received new diagnoses as a result of the test. There were 10 cases where diagnosis was directly attributed to starting new treatments, discontinuing unnecessary medications or avoiding invasive procedures.
One advantage of the new test is that it can be ordered routinely. It has been used in over 180 patients at Children's Mercy since it was introduced in January 2013. The test looks at the genetic history of the patient's family, tests large numbers of genes, and combines the data with bioinformatic analysis. The test is highly sensitive, detecting approximately 95% of known genetic mutations in more than 750 diseases. Most of the genes on the panel are autosomal recessive, with few exceptions. The panel is rich in genes for neurodevelopmental, metabolic, nuclear mitochondrial, intellectual disability, and immunodeficiency conditions.
Stephen Kingsmore, MB ChB, DSc, director of the center for Pediatric Genomic Medicine at Children's Mercy, said, “There are about 7,000 diseases caused by single-gene mutations, about half of which have identified genetic causes. Genetic testing in critically ill babies might be able to identify the cause, but prior to development of this new approach, gene sequencing took too long, cost too much, and the findings were too complicated for practical use. This new diagnostic system currently includes signs and symptoms for 595 single-gene diseases for which the causes are known.” The study was presented at the 63rd Annual Meeting of the American Society Genomics (ASHG) held October 22–26, 2013, in Boston (MA, USA).
Children's Mercy Hospital