Genetic Testing for Rare Diseases with Geneticist, Debra Regier, MD

In a recent webinar hosted by the National Organization for Rare Diseases (NORD), geneticist Debra Regier, MD, director of genetic and genomic education at Children’s National Rare Disease Institute in Washington, DC, delved into the importance of genetic testing in the realm of rare diseases. Specifically, Dr. Regier provided listeners with an overview of the different types of genetic tests, indications for their use, as well as their benefits and limitations.

Following a brief overview of basic biology in genetics, Dr. Regier homed in on classical genetic syndromes and explained how approximately 80% of rare diseases are genetic. A variety of different tests are used, depending on the rare disease. Karyotyping, sequencing, next-generation sequencing, and SNP chromosomal microarray (CMA) are the most frequently used genetic tests. In the last several years, whole exome sequencing (WES) has become an important testing strategy. Just recently, the role of whole genome sequencing (WGS) has begun to emerge in clinical care.

WES and WGS can span 98% exon coverage, with WES having >100X depth and WGS having >30X depth, but costs of both tests are high. The success rates for WES is about 25% and WGS is expected to increase this to about 30%. The costs of both tests are higher than that of traditional DNA-based testing. Dr. Regier also mentioned that different insurance companies and states cover different tests at different amounts or not at all. That being so, it is important that patients work with a provider and their insurer to identify the most cost-effective approach to a diagnosis.

High costs aside, Dr. Regier also mentioned how there is a 40% chance that a geneticist can help a patient find a diagnosis. Although the percentage may sound low, according to Dr. Regier, this success rate is actually pretty high. For families without a diagnosis, following with a rare disease specialist can also be helpful, since many of the resources for diagnosed patients can also be available for non-diagnosed patients that can improve quality of life. In addition, this team can help the patient to feel less alone in the diagnostic odyssey.

Despite its burdensome costs, genetic testing can often prove to be life-saving, as was the case for Bailey, a patient with spinal muscular dystrophy (SMA). Thanks to genetic testing, deletions in the SMN1 gene on chromosome 5 were detected in Bailey’s genetic makeup, leading to an SMA diagnosis and qualification for a life-saving clinical trial.

Genetic testing also changed David’s life, another patient, by correcting a misdiagnosis. Originally diagnosed with idiopathic peripheral neuropathy, sequencing testing showed David to actually have adult polyglucosan body disease (APDB). This testing also allowed David to receive a proper diagnosis, and thus, appropriate treatment for his condition.

While the need for proper diagnoses and appropriate treatments send many rare disease patients to call for genetic testing, concerns over privacy have also derailed some. As Dr. Regier shared, a patient’s medical history is not kept 100% private when it comes to genetic testing. She explained how the issue of working with an insurance company is that medical information has to be shared with the testing company in order to have the test approved; however, the shared information is limited.

Although DNA sequences cannot be shared without a patient’s permission, the company can share information within the company’s own group, but, again, there are limitations. Although the company is limited to what other purposes it can use the medical history for, it can submit the information to certain databases.

Looking past the weighted pros and cons of genetic testing; however, Dr. Regier drove home the importance of genetic testing and the opportunity it provides for patients with rare diseases. She recommended that rare disease patients seek either a geneticist like herself or a genetic counselor to both inquire about testing and to cope with receiving a diagnosis. “There are a lot of emotional issues and psychosocial issues,” she said, “and genetic counselors are pivotal in that care.”