Detecting Rare Disease-Causing Glitches

For people with suspected rare genetic conditions, getting an accurate diagnosis can be difficult and frustrating. A new study suggests that a fast, powerful technique called whole-exome sequencing can help doctors pinpoint the causes of many hard-to-diagnose genetic conditions.

Understanding the cause is crucial for developing a treatment plan. It can also help the family understand the risk to other members.

Instead of sequencing the entire human genomeThe entire set of genetic instructions in your body., which has 3 billion DNA base pairs, whole-exome sequencing focuses on just 1%. The exome only includes regions that code for proteins—where many disease-causing glitches are found.

In 2 NIH-supported studies, research teams analyzed the exomes of a total of nearly 3,000 people who were thought to have a genetic disorder. Most were under age 18. In many cases, their parents’ genetic sequences were also assessed. Some of the patients had gone through years of consultation and testing, but none had yet received a definite diagnosis.

Both studies found that whole-exome sequencing led to a potential molecular diagnosis for about 1 in 4 participants.

More studies will be needed to confirm these findings. Further work will also be needed to assess how whole-exome sequencing can best be applied in the clinic.

“I expect that in a few years, we’ll learn of the importance of whole-exome sequencing in adult medicine and in pediatric fields outside of development,” says Dr. Sharon Plon of Baylor College of Medicine, a coauthor of one study.