Last week Garreth and I sat down for a science class with Aidan’s fabulous geneticist. She’s been following Aidan’s progress since birth and has already tested him for many genetic anomalies. A specific lab is offering full exome sequencing at no cost to us. This will be the most complete look at Aidan we can get right now and may give us some insight into his specific medical issues.
I’m going to refrain from giving you the full on science of what we learned because I’d probable screw it up because our bodies are so amazingly complex and this test is so very detailed and the field of genetics is constantly changing.
Here are the basics; please take this with a grain of salt.
The exomes are the protein coding part of your genes, and though the exome is just a small portion of the entire genome, the exomes are responsible for most disease causing mutations.
First the lab will look at Aidan’s exomes. They will look for suspicious deletions, duplications, or sequencing issues. They will sequence specific exomes that are known to cause medical issues related to Aidan’s neurological and developmental issues. They will also look at exomes that could reasonably be expected to cause disease.
They will find variations, possibly thousands of them. We all have mutations that actually have no impact on our health. They need to figure out if any of these exomes, or perhaps combination of exome mutations could be causative in nature for Aidan. It’ll be an interesting hunt.
They will compare Aidan’s exomes to a control group and, or course, to us, his parents. They will find extra genetic material on his third chromosome and then they will find it on mine because it’s shown up in previous genetic testing. Because it has caused no medical problems in my body, it’s not the source of medical problems in his. They will look for something that shows up specifically in Aidan that doesn’t show up in us, or possibly a strange combination of mutations that he received from Garreth and I that possibly caused a perfect storm.
Here’s where it gets sticky. We signed a consent form that gave them permission to look specifically at genes that are known to cause certain diseases that can be prevented or treated. (Think Angelina Jolie and the BRCA breast cancer gene.) These genes won’t give an answer to Aidan’s diagnosis but may give us useful information regarding Aidan’s general health. For example, there is a gene mutation that will only effect you under anesthesia. That’s very specific and rare but it could be deadly when it’s very preventable. Aidan most likely doesn’t have this because he’s successfully been under anesthesia several times, but he will have more surgeries in his lifetime and this is helpful information. Because Aidan is non-verbal and can’t give us specific indications of pain or illness, we want whatever information we can get about his health risks.
If he is found to have any of these disease causing genes, they would look at our blood samples to determine if Garreth or I have them as well. Garreth and I do not walk away with a clean bill of health because they are only looking at our sequences as they relate to Aidan. I will not be certain if I carry the BRCA gene, for example, unless Aidan does because they will not look specifically at Garreth and me without cause.
It’s all very fascinating. Aidan may or may not come away with a diagnosis. He could have a very rare combination of gene mutations that little is known about. He could have a very specific mutation that has no treatment indications. I’m ok with all of that. Twelve years later I’m in a very different place then when Aidan was born. I know we’re not alone in being undiagnosed; I know that he will continue to make progress; I’m more comfortable with his required level of care. It’s been an emotional roller coaster and I can’t quite anticipate where I’ll be with all of this in another decade.
For now, I hope this science helps the next baby who lands in the NICU without a diagnosis.