Whole-Genome Sequencing, Aided by Bioinformatics Analytical Software, Offers Quick, Accurate Test for Diagnosing Diseases Caused by Single-Gene Mutations
A new approach to genetic testing of critically ill children, developed by researchers at Children’s Mercy Hospital, can be a road map other medical laboratories can follow
In Kansas City, a medical team at Children’s Mercy Hospital has demonstrated that rapid whole human genome sequencing, when combined with interpretative software, can return clinically actionable answers quickly enough to be of value to physicians who are diagnosing patients showing symptoms of genetic conditions.
As many pathologists and clinical laboratory managers know, childrens’ hospitals across the nation are often at the vanguard of using molecular diagnostics and genetic tests to guide diagnosis and treatment of pediatric patients. Having the capability to make fast and accurate diagnoses of genetic conditions gives physicians at these institutions the ability to significantly improve the outcomes of their patients.
Approach Combines Rapid Genetic Sequencing with Interruptive Software
Advances in gene sequencing technology now make it possible to deliver results in ever shorter periods of time. This capability can return a correct diagnosis in just 50 hours, markedly quicker than current genetic testing, noted Stephen Kingsmore, B.Sc., M.B., Ch.B., B.A.O., Director of the Center for Pediatric Genomic Medicine at Children’s Mercy Hospital and Professor of Pediatrics and Obstetrics & Gynecology at the University of Missouri Kansas City School of Medicine. Kingsmore led the research team that developed this diagnostic system.
The new approach combines rapid genetic sequencing with software that provides interpretation of the findings. It could “transform the world of neonatology,” Kingsmore said at a teleconference with reporters, noted the medpagetoday.com report.
Symptom- and Sign-Assisted Genome Analysis software, or SSAGA, focuses clinical attention on particular genetic regions linked to specific symptoms, while Rapid Understanding of Nucleotide-variant Effect Software, or RUNES, characterizes their functional effect, explained Neil Miller, Children’s Mercy Director of Informatics and Software Development.
Rapid Gene Sequencing Contributed to Diagnosing Tay-Sachs Disease
In their pilot study, published in the American Association for the Advancement of Science journal, Science Translational Medicine, this diagnostic system correctly identified cause of death in two babies, one with Tay-Sachs and the other with Menkes disease. In a prospective research protocol, it definitively diagnosed four out of five children affected by a genetic disease.
There are about 7,000 diseases caused by single-gene mutations, about half of which have identified genetic causes, Kingsmore said. He noted that 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. Researchers are currently working to identify and add other genetic diseases and conditions.
While this test is costly at about $13,500, the cost is relatively inexpensive considering the daily rate for neonatal intensive care is $8,000, said Kingsmore.
More recently, Kingsmore’s research team has developed a more cost-effective screening test for more than 750 genetic diseases, according to a press release issued by Children’s Mercy. Called TaGSCAN (Targeted Gene Sequencing and Custom Analysis), the test costs just $3,200. Among diseases this screening test can identify are muscular dystrophy, cystic fibrosis, polycystic kidney disease, as well as hundreds of diseases that have either been challenging to diagnose or for which no test has been available.
Genetic Screening Test Results Presented at ASHG Scientific Meeting
A product of Children’s Mercy’s Pediatric Genome Medicine research, TaGSCAN was presented at the American Society Genomics (ASHG) 63rd Annual Meeting in October. The presentation, “Utility of a Strategic Next-Generation Sequencing Approach to Genomic Diagnosis of Patients with Neurodevelopmental Disorders,” included a study involving 107 patients with neurodevelopmental disorders. Forty 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.
“Our findings include real-world examples of how this new technology has impacted patient care,” Sarah Soden M.D., a Developmental Pediatrician at Children’s Mercy and Associate Professor of Pediatrics at University of Missouri-Kansas City School of Medicine, told the ASHG gathering. “By identifying the cause of previously undiagnosed diseases, we are giving families answers they have been searching for—answers that will hopefully improve their children’s lives.”
Children’s Hospitals at Cutting Edge of Genetic and Molecular Diagnostics
Children’s hospitals are often at the forefront of molecular diagnostics and genetic testing because they understand the clinical and financial benefits that result from the ability to make a faster and more accurate diagnosis of a patient they will treat for years to come. Further, these hospitals consider that their advanced diagnostics capabilities are a competitive advantage and distinguish them as innovative centers of clinical excellence.
Those medical laboratory managers and pathologists who want to stay abreast of developments in rapid whole genome sequencing for clinical purposes would do well to keep an eye on childrens’ hospitals in their communities and surrounding regions. As shown by the work done at Children’s Mercy in Kansas City, new doors are opening for the use of whole genome screening for clinical purposes.