Cristy and Rick Spooner of Rancho Santa Margarita, Calif., spent 14 years trying to solve a heartbreaking mystery: What caused the severe disabilities that plagued two of their three daughters? Baffled doctors couldn’t determine why the sisters had seizures and why they failed to learn to talk, walk or reach other developmental milestones. Even a brain biopsy on the oldest daughter yielded no clues, which led Cristy Spooner to lose faith in doctors.
However, everything began to change for the Spooners in October 2012. That’s when a geneticist whom they had seen years before contacted them to let them know about a new test that would allow scientists to analyze from a blood sample a broad segment of their children’s DNA to determine whether a disease-causing mutation existed. In February 2013, weeks after the girls’ blood was drawn for the tests, their diagnostic odyssey ended when scientists discovered that the girls inherited a rare genetic mutation that causes a disorder in how their cells function.
The technology that was used to test the Spooner girls, which is known as next-generation sequencing, represents a new chapter for diagnostic science that for years also has been used to predict whether adults who have a family history of cancer or Alzheimer’s disease are likely to develop such diseases. For instance, everyone knows about movie star Angelina Jolie’s decision to have a mastectomy in 2013 after a genetic test revealed that she faces a high risk of getting breast cancer.
Next-generation sequencing examines important portions or all of a patient’s genetic code rather than just a single gene, as Jolie’s test did. Consequently, scientists and doctors now can cast a much wider diagnostic net than previously. This is particularly useful in cases where children have a rare disease. Furthermore, the cost of next-generation sequencing and the time that’s required to get results from it have decreased dramatically in recent years.
In extreme cases, next-generation sequencing can lead to miraculous cures for extremely sick children, experts tell Consumers Digest. In other cases, as the Spooners discovered, the test at least can determine the cause of problems even if a cure or a treatment doesn’t exist. However, studies indicate that the vast majority of children who are sequenced get no diagnosis, which is why health-insurance companies frequently deny coverage. As a result, parents could shell out as much as $7,000 for the test yet feel the frustration of still having no answers.
Furthermore, three experts whom we interviewed warn that, by peering into such a broad section of a child’s genome, doctors have the potential to open a Pandora’s box of unintended findings that have medical, emotional and financial consequences for the children and their parents. Doctors today don’t sequence healthy children, because medical ethicists and physicians groups believe that the test should be used only to diagnose illnesses rather than to predict what diseases a child might encounter when he/she is an adult. However, some experts say it’s only a matter of time before the test becomes available to all children and adults.
TEST PATTERN. A genome is the com-plete map of a person’s DNA, including all of his/her genes. DNA is made up of at least 3 billion so-called base pairs of chemicals, which make the proteins that make you who you are. When any one of those bases is deleted or repeated, or its order is switched around, it’s called a mutation, which can cause a disease. Reading, or sequencing, a genome allows scientists to try to identify mutations.
The first sequence of the human genome took 13 years and cost $3 billion before it was completed in 2003. A few years later, next-generation sequencing technologies were developed, and they allowed scientists to sequence people more quickly and for less money than did previous sequence tests. In 2009, scientists used next-generation sequencing to target only a section of the genome rather than the entire genome to make a genetic diagnosis. This approach can cost as much as 10 times less than a complete sequence does. The more targeted test is called whole-exome sequencing, while the broad test is called whole-genome sequencing, but, in this article, the term next-generation sequencing applies to both tests.