Whole Exome Sequencing

Do you remember way back in September when I wrote about Zack having Whole Exome Sequencing done at Walter Reed?  No?  No worries, I can barely remember September either…

Let me refresh your memory.  We were told that though this test looks at over 20,000 genes, positive results are only found 30-40% of the time.  This is true even when the person being tested has significant medical signs and symptoms.  Even so, together with Zack’s doctors, we decided to see if this test could find a reason for Zachary’s issues.

When we heard the results were back in only three months, we tried really hard not to get our hopes up.  Jim was not able to go to the appointment with me this time, but we were able to have him listen in on my cell phone as Zack’s geneticist gave us the results.

Are you sitting down? I really think you need to be for this.  Zack’s testing results came back positive for an anomaly.  Not only that, his doctor told us that he felt the anomaly was the reason for Zack’s intestinal problems!  He seemed pretty excited about that and rightfully so!  Many doctors in several hospitals have been working for many years to try to figure out what on earth is wrong with our boy.

And now for the moment you have all been waiting for…oh wait….I guess only Jim and I have been waiting for this moment.  But I’ll share it with you as well.  Here are the results of Zack’s test:

1.  Causative Variants in Disease Genes Associated with Reported Phenotype:

  • Gene – ACTG2
  • Disease – ACTG2 – Related Disorder
  • De Novo – new to Zack (Jim and I do not have this mutation.)

2.  Zack’s variant in the ACTG2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. (Zack is the first documented person with this variant….of course…) This variant is not observed in large population cohorts. We interpret (Z’s variant) as a likely pathogenic variant, which is likely consistent with the megacolon, small bowel obstruction, dysmotility, and constipation reported in this individual.

You may be wondering what on earth that really means and so do we.  It has only been about 36 hours since we found out.  We left the doctors office armed with many articles to read, websites to look up, and information on some organizations that deal with gastrointestinal diseases that we had not heard of before.

This is what I can tell you.  This is from the NIH website:

The ACTG2 gene provides instructions for making a protein called gamma (γ)-2 actin, which is part of the actin protein family. Actin proteins are organized into filaments, which are important for the tensing of muscle fibers (muscle contraction) and cell movement. These filaments also help maintain the cytoskeleton, which is the structural framework that determines cell shape and organizes cell contents.

The γ-2 actin protein is found in smooth muscle cells of the urinary and intestinal tracts. Smooth muscles line the internal organs; they contract and relax without being consciously controlled. The γ-2 actin protein is necessary for contraction of the smooth muscles in the bladder and intestines. These contractions empty urine from the bladder and move food through the intestines as part of the digestive process.

You can read more about ACTG2 on the website and look up health conditions commonly found with genetic changes on the gene.  One of the interesting things we read in one article is that periods of severity can wax and wane.  Zack often has periods of intestinal obstructions in his small bowel.  Thankfully, they have been resolving on their own lately.  However, he definitely has periods of more intense pain, prolapsing and obstructing.  We also think this may explain why he had normal motility testing and then a few months later his testing showed complete dysmotility.  A year after that his testing showed zero motility once again.  Soon after that he had his final motility testing which showed that he had a few centimeters in his colon with motility.  Craziness.  It may also explain Zack’s urine retention issues after surgery.  These always result in bladder scans and the threat of catheterization.  We need to discuss these things further with his GI doctor.

Zack’s geneticist said that people usually have one of two reactions to news of genetic anomalies.  They either express great relief or sadness.  I think I experienced some of both, but mostly great relief.  Knowing that Zack’s condition is not “curable” is actually helpful, in my opinion, because it rules out a lot of testing and guessing about next steps.  The sad part about this is that when we told Zack that the doctors found a reason for his intestines misbehaving, he was excited.  He said, “Yay!  Now I can be cured!!”  That was a bit of a tough conversation, but only for like two minutes.

Jim and I will have an appointment with Zack’s GI to discuss plans going forward in mid December.  We have many questions and I am sure his doctor does as well as this is new information for all of us.  Until then we will be researching and reading all we can about ACTG2.

I leave you with a photo of our crazy family over Thanksgiving weekend trying to get that oh.so.elusive Christmas card photo.  Jim’s face reminds me of Steve Martin in Father of the Bride and totally cracks me up.  He says he was just checking to make sure Zack was OK.  The boys and I were laughing like crazy because Zack was being a goofball.  Good times and great memories of our last time together at home before Drew gets married!

Hug your babies!

~ Dawn

2 thoughts on “Whole Exome Sequencing

  1. Wow! Thanks for sharing all this.
    It’s really a lot to try to understand and process, but as you have said……at least you now know the what’s causing the problems.
    I admire your family’s courage and persistence. I’m hoping and praying that although his condition is incurable, at least, am hoping that a way may be found to comfortably cope with it. . It’s all pretty scary to me. I can only imagine how you must be feeling.
    Sending much love…

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