Help for People Battling Undiagnosed Disease 

By Steve Spencer

As a non-profit, HudsonAlpha (HA), located in Huntsville, is a global leader in biotechnology and genomic research. HA scientists have made discoveries in ALS, childhood genetic disorders, and kidney cancer. They’ve expanded research in bipolar and schizophrenia and are conducting ongoing investigations in a number of disease states, including cancer, Parkinson’s, lupus, and multiple sclerosis.

In an effort to put their expertise to use for the general public, in 2015 HudsonAlphaHudsonAlpha founded the Smith Family Clinic for Genomic Medicine. “The clinic opened with the idea to be the first stand-alone genomics clinic in the nation,” said Meagan Cochran, MS, CGC, the Director of The Smith Family Clinic. “We wanted to focus on genomics as this idea behind solving undiagnosed cases of suspected genetic disease.”

The clinic provides genetic counseling to patients with an existing diagnosis or family history of disease; administers tests for women who plan to become pregnant; But their largest patient group is made up of people who are battling a disease without a diagnosis, people for whom there has been no effective treatment and no answers.

“We see everyone from babies to senior citizens, all of whom have some suspicion of an underlying genetic disease that might explain some of the symptoms they’re having,” Cochran said. “In the pediatric space, most of our patients have some sort of neurodevelopmental differences, things like developmental delay, autism, intellectual disability, as well as children born with physical birth differences.

“And as we go on through the lifespan, things might look a little different. We see plenty of adults who were healthy until they weren’t. Maybe they developed some sort of adult onset neurological disorder or cardiac condition. But something about it has triggered their healthcare team to wonder if this could have a genetic cause. And that’s how they get to us.”

A clinical geneticist and/or a genetic counselor will see the patient, and evaluate their symptoms to determine what genetic test is appropriate. “Sometimes we’ll only need to order a relatively simple genetic test, maybe taking a closer look at their chromosomes or doing a set of genes that are all connected to one particular type of disorder,” Cochran said. “But there are other times when we see a person, and we’re not really sure what it is. In that case, we might go wide and do genome sequencing or reading through all of the DNA to try to get to an answer.”

While there are many genetic variants in which the symptoms are obvious from birth, researchers are still working to understand how a person can be healthy until a disease emerges later in life, even though the DNA difference was there the whole time.

“A person can be born with some level of genetic risk for a given disease,” Cochran said. “It’s not due to any one particular gene. It may be a combination of variants which you can’t change. But you can change things like your lifestyle. Imagine a jar that you have to fill up in order to have the disease. So you’re born with your jar part of the way full thanks to your DNA. But can you add or take things out of your jar based on your lifestyle? For example, with diabetes, things like a poor diet would add to your jar. On the other hand, good exercise would subtract from your jar.”

Even though the field of genomics has achieved extraordinary advances in the last two decades, there are still limitations. “Over the last 10 years, we’ve sequenced 2,000 people who have some sort of suspected rare disease,” said Susan Hiatt, PhD, a research faculty investigator at HudsonAlphaHudsonAlpha. “Yet, in our studies and across the United States, there are only about 50 percent who get a diagnosis. Many times, we know there is something in the genome affecting their disease, but we haven’t been able to find it. There are still a lot of genes that have not yet been described as disease genes.

“And while we think that genome sequencing is the most comprehensive test, it still has its limits, particularly where there are repetitive regions of the genome. There are a few new technologies that do longer read sequencing which are helping to identify some of these odd looking changes in the genome that we don’t understand as well yet. In fact, we just published a study in which we took a number of programs where we had previously done a short read sequencing, and we then did a long read. In about 10 percent of them, we found something that we couldn’t see before. The long read sequencing can also detect epigenetic changes which could provide a lot of good information in the future.”

If you’d like to help people who are suffering through undiagnosed genetic disease, you can donate to the Hero Fund, which was established through the HudsonAlpha Foundation to help patients who can’t afford it, get access to genomic medicine. You can find it at www.smithfamilyclinic.org/hero.