Next-Gen Sequencing: Expanded Genetic Testing in the Real World

Marshall L. Summar, MD; Brendan C. Lanpher, MD; Sean E. Hofherr, MD


September 15, 2014

Editorial Collaboration

Medscape &

In This Article

Who Should Be Using Next-Generation Sequencing?

Dr. Summar: Any time a new technology comes along, many people are interested in using it. Who should be using this test?

Dr. Lanpher: It's very important that people with expertise in genetic diagnosis and interpreting genetic results are ordering these tests and reporting these test results to patients and their families. This is not a first-line test. It is done after a very careful history, examination, and assessment for dysmorphic syndromes. It is useful when more targeted testing has been done and is unrevealing, or when such testing can't be done. We have used it on quite a few families in our clinic. We have made diagnoses with it. We have also had the experience of the test not providing a diagnosis.

Dr. Summar: What proportion of the time is it useful?

Dr. Lanpher: In our hands, about 10%-15% have led to a confirmed diagnosis.

Dr. Summar: Are those patients who have been evaluated by an experienced geneticist and typically referred from a primary care provider or another specialist?

Dr. Lanpher: That's right. These patients are on that diagnostic odyssey. They have been through many previous tests that haven't been revealing. We have had the situation in which patients have had abnormalities on earlier tests that explained part, but not all, of the phenotype, and we have gone on to whole-exome sequencing. Sometimes, those previously identified mutations have been seen, and sometimes they haven't been seen, which is partly what gives us pause about next-generation testing. It is an important tool in our repertoire, but it does not replace more targeted testing and a careful examination and history.

Dr. Summar: Who should be using it?

Dr. Lanpher: Genetic professionals should be using it.

Dr. Summar: What about other fields? Obviously there is a lot of interest, and many people want to reach for this test. It's being marketed that way, too. Who should be cautious about using it?

Dr. Lanpher: Everybody should be cautious about using it. Even geneticists should be cautious about using it. The potential for physicians, families, or patients to misunderstand results is very high. These results are difficult and challenging to deal with and to understand. Even from the best labs, which write very nice reports, these results can be very challenging to interpret.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.