In the typical anal retentive mode that I function I got the test results early from the doctor. I mean I can basically read the results as well as the doctor. Interpreting the results are harder for me but it allows me time to read the results, digest the information and then formulate questions to ask the doctor when we meet on Monday. The results were what I feared... Joseph once again leaves a BIG FAT QUESTION MARK behind in his wake!
We started this test on May 6th. All of us went to get our blood drawn. This would allow more samples to be available to be compared to Joseph's. I waited for SIX months to get the results back from the whole exome sequencing. So here is what the results page of the test reads. Keep in mind that 97% of Joseph's DNA was analyzed to determine these results...
- No definitive explanation for the cause of the phenotype in this patient was identified by this analysis.
- Variants in genes possibly associated with the reported phenotype: Heterozygous for the R854Q mutation in the vWD gene. (I looked this one up. It's von Willebrand disease.)
- Variants in the candidate genes with a potential association to the phenotype:
- Heterozygous for the V759M and E826K variants of unknown significance in cis in the MICALL2 gene
- Compound heterozygous fit D3110N and W3598X variants of unknown significance in the SPTBN5 gene.
The good news is that the ACMG was clear. That looked for known genetic markers that are a danger to your health. Most of these genes are cancer related. That's really good news for all of us because we elected to know if any of us were a carrier.
The interesting news is that Joseph and I have a genetic variation for von Willebrand disease. This genetic mutation (R854Q) is a common mutation found in Italy. Also found in a population in Wales. As far as our family tree goes we do have known family ties to Scotland.
The other gene mutations the report said that V759M is pretty unknown. The E826K has been linked with a significant reduction in the cAMP-induced chloride current in cystic fibrosis patients. It does not sound good. I found a BRAND new research article discussing cAMP chloride transport and the neurites of brain cells. I know one of the mutations mentioned discussed how neurites are under active. From what I can tell neurites are the pokey parts of cells. Then the other mutation reduces the cAMP pump. What if this is why Joseph is so mentally slow? The neurons in his brain do not have the neurites as long as they should be while the cAMP pumps are not pushing out the signal from the neuron. Maybe the neuron's signal is getting lost from one cell to the next?
The D3110 gene was associated with squamous cell cancer of the lung. My grandfather on my mother's side died of lung cancer when I was 18 or 19. He was a smoker but I know he did not die of any kind of lung cancer that is typically associated with smoking cigarettes. I will have to follow up with my mother and try to get more information.
The W3598X has no information on it to compare. I will have to look for more information.
The SPTBN5 has an paralog gene called ACTN4. ACTN4 is associated with a couple of rare diseases. One of these is Focal Segmental Glomerulosclerosis (FGS). A lot of the problems Joseph has are symptoms of this disease such as intellectual delay, hypotonia, constipation, undescended testes, and hernia.
Interesting stuff and I will be interested to see what the doctor says. Even more interesting will be me presenting him with the research I have found so far and the questions I will have for the appointment!