A new UCLA Health study examined the effectiveness of genetic testing to diagnose neurologic conditions in people who had never been tested because of access barriers.
The paper, in the journal Neurology Genetics, concluded that nearly 43% of study participants whose doctors recommended genetic testing faced insurance-related hurdles.
Brent Fogel, MD, PhD, professor of neurology and human genetics at the David Geffen School of Medicine at UCLA, said a genetic diagnosis can shape medical care and end the lengthy and expensive quest for the cause of a condition.
“In some cases, the diagnosis can lead you to a specific treatment you might not have otherwise pursued or lead to testing for an associated condition you might not have been aware of,” he said. “For some rare conditions there might be a clinical or research trial you can get involved in. Of course, children and other family members will also likely want to know if they are at risk.”
Dr. Fogel, corresponding author of the study and co-director of the UCLA Clinical Neurogenomics Research Center, said researchers performed exome sequencing, a type of genetic testing that sequences the coding portion of all 20,000 genes in the human genome, for nearly 300 people with suspected neurogenetic conditions. They also looked at why participants had never been tested in clinic before.
In all, 16% of participants received a diagnosis. Among them, 30% had previously forgone testing for insurance-related reasons.
Insurance barriers included outright denials, inadequate coverage or the inability to find out in advance if the test would be covered.
“One of the things that we encounter in clinic quite a bit is insurance payers denying access to genetic testing to patients for various reasons,” Dr. Fogel said. “The challenge we’ve faced is what evidence can we cite to tell the payer they need to cover this test?”
Genetic testing
Exome sequencing covers the entire human genome, but only analyzes the protein-coding portion where most mutations are found. It sequences about 20,000 known genes, looking for more than 7,000 genetic conditions.
Exome sequencing can diagnose certain neurogenetic conditions that cause intellectual disability, muscular dystrophy, epilepsy, dementia or cerebellar ataxia, which is the loss of balance and coordination.
“Sometimes a neurological problem will run in the family, suggesting it is very likely genetic,” he said. “When something genetic is suspected, that’s when your doctor may order tests such as this.”
Dr. Fogel said exome sequencing will result in a diagnosis roughly 25% of the time. The number may sound low but is actually high as far as medical tests go, he explained.
“Not every mutation will be detected by this test,” he said. “Some mutations may occur in genes that we don’t know are disease genes yet, so we don’t how to interpret those. Sometimes there are limits to our knowledge about specific genes. For example we may see a variant we think might be related but we can’t prove it.”
Exome sequencing costs vary depending on the laboratory, but typically range from a few hundred to a few thousand dollars, Dr. Fogel said.
Seeking answers
UCLA Health researchers teamed up with , a company specializing in genetic testing for rare diseases. The study tested DNA samples of 297 people, mostly adults, who were referred for exome sequencing but had never done so.
Researchers found that 47 people or nearly 16% received a diagnosis. The most common finding, for 8 people, was a gene associated with a form of hereditary spastic paraplegia, which causes muscle tightness and weakness.
An additional 24 people, or 8% of participants, had variants of uncertain significance. In all, 71 people, or 24%, had a clinically relevant result, the study found.
For the 2 out of 5 eligible patients in the study who were advised to undergo exome sequencing, insurance barriers were varied.
“The most common barriers were that insurance companies wouldn’t preauthorize the test or they would say exome sequencing wasn’t a covered benefit,” Dr. Fogel said. “Following that were claims that the test isn’t medically necessary or it doesn’t improve health outcomes. These are very common reasons for denial of genetic testing, but they’re incorrect, outdated, and archaic. This is testing patients need access to.”
Dr. Fogel said in his experience seeing patients, about half of are denied genetic testing and only about 25% of appeals are eventually approved.
In the study, some older adults didn’t undergo testing because of uncertainty over their Medicare benefits. Dr. Fogel said Medicare doesn’t provide a preauthorization, meaning patients are financially responsible if the test isn’t covered after its performed, which most patients are reluctant to agree to.
Dr. Fogel noted that barriers not outlined in the study also likely exist. He said the researchers didn’t have a large enough sample size of patients to examine if racial or ethnic disparities limited access to genetic testing.
“I suspect these barriers exist as well, but our study was not able to address that,” he said.
Other UCLA Health researchers who worked on the study are: Sonya Watson, Kathie J. Ngo, Hannah A. Stevens, Darice Y. Wong, PhD, and Clara Lajonchere, PhD.
