Exome Sequencing Improves Ability to Diagnose Neurogenetic Disorders

	Illustration: Maja Moden

UCLA researchers have found that a state-of-the-art molecular genetic test greatly improves the speed and accuracy for diagnosing neurogenetic disorders. The discovery could lead to better care for people with rare diseases like spinocerebellar ataxia, leukodsystrophy and spastic paraplegia. The test, called exome sequencing, involves determining the order of the genes in a person’s genome. When used in concert with a patient evaluation and family medical history, the approach can help doctors identify disorders that may have gone undiagnosed for years, says Brent Fogel, MD (RES ’07, FEL ’09), PhD, director of the UCLA Neurogenetics Clinic and associate professor of neurology and human genetics.

Exome sequencing is more efficient and less costly than the type of genetic testing that has been more commonly used, Dr. Fogel says, and a proper diagnosis can end what for many patients is an agonizing journey just to find a name for their conditions. The growing body of evidence supporting the use of the test, and the demonstrated benefits to patients, should lead to greater insurance coverage of the test, he says. “Despite extensive literature supporting the use of this technology, many insurance companies still consider it to be investigational and may refuse coverage. Our article outlines the appropriate use, benefits and limitations of exome sequencing that these companies need to consider when making coverage decisions.”

UCLA has been a leader in using the test as a diagnostic tool since 2012. Dr. Fogel and his team were among the first to adopt the technology for routine neurological practice, and he has been a strong advocate for wider use. Dr. Fogel and his colleagues wrote a study in 2014 about exome sequencing that was published in the Journal of the American Medical Association Neurology. That research found that 20 percent of a group of people with spinocerebellar ataxia could be diagnosed immediately using the technique. Additionally, they discovered that useful genetic information could be identified in more than 60 percent of the subjects, regardless of their age when the disease began or their family history.

Clinical Exome Sequencing in Neurologic Disease,” Neurology Clinical Practice, April 2016