At Courtagen, we offer DNA testing that uses next generation sequencing to diagnose neurological, mitochondrial, and other disorders. Because the brain and mitochondria are so complex, many of our panels have a thousand genes or more.
Each of our tests search for variations in a patient’s DNA that are likely to cause their condition. However, each of us has thousands of DNA variants, and most of them do not cause disease! So, finding the “right” gene or variant can be tremendously challenging. One of the most helpful things that a patient can do to help us evaluate whether a variant is disease-causing is to send us specimens from the patient’s parents. This allows us to sequence all three individuals and gain insight into the significance of each variant.
Why do we ask for samples from parents?
A general rule we use to evaluate variants: If a variant is present in affected patients and absent in unaffected family members, it is more likely to cause the disease.
To understand the significance of a variant in a patient, we also review information about the variant that has been reported in the scientific literature and entered into databases with the DNA sequences of healthy controls. When we sequence a patient’s parents’ DNA, we can evaluate the variant at a family level. Knowing if the parents have the same symptoms as the child is very important for this step.
For example, Grace is a child who was seen by a pediatric neurologist for seizures and global developmental delay. Neither of her parents share her symptoms. Genetic testing finds six variants that may be responsible for her seizures (see below).
In this example, the most significant variant was identified as KCNT1 because it was not seen in either of the patient’s unaffected parents. We know, from scientific research, that new variants are a fairly common occurrence in genetic disorders that affect children (R. Acuna-Hidalgo, 2016). The other variants were seen in either the mother or father, and we can rule them out.
In some families, there are multiple people affected. In these cases, we expect to find the same variant in all of the family members who have the condition. Conversely, we would expect the variant to be absent in the family members who do not have the disorder.
Sequencing a patient’s parents can also help us better determine the likelihood that the couple will have another affected child.
For example, Glenn is a child with developmental delay who has two variants in the same gene. If Glenn inherited one variant from each parent in the gene that causes his disease, the chance of his parents having an affected child in the future is 25% with each pregnancy.
What is the Triome Test?
Courtagen recently started offering next generation sequencing panels for intellectual disability (devSEEK® Triome) and epilepsy (epiSEEK® Triome) that harness the power of parents to better interpret the DNA variants we find.
For Triome tests, we require samples from the child and both biological parents up front. This allows us to look at the inheritance of all of the rare variants that are present in the child.
Prior to offering the Triome tests, we would request parent samples once variants were identified and after the patient report was issued. This stepwise approach often added weeks to the amount of time it took to get a final answer. By testing the parents at the same time as the child, our epiSEEK Triome and devSEEK Triome tests streamline the process and speed up the time for getting back the final test results.
We encourage you to contact us with any questions about our Triome or other genetic testing. Please use the form on this page to get in touch!
- Acuna-Hidalgo R, Veltman JA, Hoischen A. Genome Biol. 2016 Nov 28;17(1):241.