Gene Sequencing May Reveal Risks for Rare Diseases

“Genome sequencing” of healthy people reveals that some are at risk for rare genetic diseases, a new study shows. And doctors need to be sensitive when revealing that information, the researchers said.

“Sequencing healthy individuals will inevitably reveal new findings for that individual, only some of which will have actual health implications,” said study lead author Dr. Jason Vassy. He’s a clinical investigator at Brigham and Women’s Hospital in Boston.

Whole genome sequencing entails analysis of the 3 billion pairs of letters in someone’s DNA. Scientists anticipate the technology will usher in a new era of predicting and preventing disease, but how people will react to this personal information is a big question mark.

For this study, the researchers analyzed nearly 5,000 genes associated with rare genetic conditions in 50 healthy people. The investigators found that 11 of the people – almost one-quarter – had gene variants predicted to cause previously undiagnosed rare disease.

Two of those 11 patients had signs or symptoms of the underlying conditions. One had variants linked to an eye disease called fundus albipunctatus, which impairs night vision. The second had a variant associated with variegate porphyria, which explained the patient’s mysterious rashes and sun sensitivity.

As part of the study, the patients’ primary care doctors were taught how to interpret a one-page report of their patients’ genome testing results. They also had access to genetic specialists for consultation. The doctors then used their own judgment in deciding how to handle their patients’ test results.



While the findings appear promising, “continued research on the outcomes of sequencing will be needed before the routine use of genome sequencing in the primary care of generally healthy adults can be medically justified,” Vassy said.

The study was published June 26 in the journal Annals of Internal Medicine.

My Take:
I have been looking at just 26 gene snippets that are sequenced through the 23andme genetic testing. These snippets look at the metabolism of vitamin B12, folic acid, neurotransmitters, hormone production and dismantling.

They provide valuable insight into the prevention of disease rather than predict rare disease onset. Lifestyle modifications can also be gleaned from this information.

For example, I have had a couple of patients where I recommended restriction of cruciferous vegetable intake as they genetically have an impaired ability to process the sulfur bearing amino acids in these foods. Conversely, I have found patients that need life-long nutritional support of these same chemical pathways. Proper sulfur amino acid metabolism is key to hormone detoxification (think reproductive cancer prevention), repair of connective tissue, and proper bowel flora (microbiome) maintenance.

There are also gene snippets that make a person more vulnerable to injury with exercise or make them more dependent on exercise to prevent diabetes.

However, my favorite is the “warrior gene”, found only on the X chromosome. Men only have one X chromosome so this gene mutation can only be homozygous in women. This gene predisposes women to depression and even suicidal thoughts, especially in their teen years. However, when women with the warrior gene have high powered occupations or are pursuing their passion, they flourish. My most recent patient with the warrior gene has quit her “day job” to pursue writing. She is following her passion and feels great.

The Bottom Line:
Genetic testing is a good tool in preventive medicine and will only become better as the science advances. The key is epigenetics – the science of gene expression rather than resignation that any particular disease will develop because of your genes.

Source: June 26, 2017 National Institutes of Health