I have been waiting for the day when I could post some news about the genetic tests that were started in March of this year. I feel the need to share all of these updates with you because it is through all of your generosity and support that we were even able to go through with this testing in the first place. While the company was incredibly accommodating by lowing the price of the testing several thousands of dollars and fighting our insurance for coverage, it was still incredibly expensive.
We met with the two doctors that oversaw the treatment of Drew while he was at Golisano's Hospital. Before I tell you what we were told, I want to put our this process into context so you understand the decisions we have had to make regarding these tests. First, we had to decide which form of testing to do. While this form of testing is brand new, has never been done this way before, and costs overwhelmingly more than the traditional method, both Robert and I felt 100% sure that it was the path to take after we prayed and fasted about it. Second, we were told that we should expect nothing. They were so unsure of wether we would get any information that they told us there was a very good chance we will get a large summary of genetic mutations that mean absolutely nothing to the scientific community....not all mutations have been discovered. We have spent the last month milling over our decision and praying that we would get even a little bit of information to explain Drew's sickness and death....we got more than just a little.
Robert is a carried for the subtype CblF disorder. (Cobalamin disorders have 8 current subtypes based on the location of the mutation). This genetic mutation is a frame shift mutation located on the LMBRD1 Gene in Chromosome 6. I am a carrier for the subtype CblG disorder; a change form mutation. Instead of a Proline amino acid there is a Leucine amino acid. It is located on the MTR Gene on the 1st Chromosome. Both mutations are common for this rare disorder and are no doubt disease causing mutations. This is where it gets a little tricky....Normally, parents carry the same subtype for this disorder. We however, do not. I have no disease causing mutations that would cause CblF and Rob has no disease causing mutations that would result in CblG.
The result of these tests, as conclusive as they were, now lead to a slew of new questions and theories. Here is the best part. Becuase they were able to determine with incredible accuracy that we are carriers for these types, they were able to secure a dry blood spot from the New York State New Born Screen lab that they preserved from when Drew was born. The same lab that performed this genetic analysis is currently calibrating a new test to use that dried blood sample from Drew and test which mutations he received from us! This is incredible news. There is a very high chance that we will be able to pinpoint exactly what happened to cause his disorder.
Because of the complexity of our situation (being carriers for two different subtypes) there are basically three theories they will be testing Drew's DNA for:
1. Drew received both mutated genes from Robert and I from the MTR gene and LMBRD1 Gene in what is called Digenic Inheritance. If this is the case, it will be the first reported case of a cobalamin disorder that occurred in a digenic inheritance pattern-a disease caused by co-inheritance of mutations at two distinct genetic loci or two different genes! This theory will prove true if they find Drew received both mutated copies.
2. During conception and the first division of cells, the two chromosomes from either Robert of I carrying the mutation did not split and resulted in having three of the same chromosome in the divided cell. In order to avoid a problem, that cell would have "kicked" out the third chromosome and left the two copies of mutated chromosome-eliminating the healthy chromosome. It is basically the same process that occurs for children with Down's Syndrome expect the third set is kept. This will prove true if Drew's sample indicates two sets of the same mutation. In that case, the chance of having another child with this disorder decreases to less than 1%. This is called uniparental disomy.
3. Drew received either the mutated gene from Robert and I, and an alteration occurred at the moment of conception, in the exact same gene as one of the other mutations.
I know this is a lot of information. You can imagine how it must have felt hearing all of this from them today. In some ways it was miraculous because we could see the Lord's hand in our life and in the decisions we have made. At the same time, we have to wait longer. We are halfway to the answer we are seeking. We do feel incredibly grateful because in all honesty, neither of us thought we would get this far. We fell to the bottom of a dark pit in the last year wondering about what our future would hold. I think we are both hoping and praying that we get the genetic confirmation from the dried blood sample they were able to obtain from Drew. Of course it would be miraculous if this circumstance ended with us having less than 1% risk with another child.
To close, I want to bring you back to the decision we made to do these tests. If we would have chosen the traditional method of testing each subtype separately, they would have never detected the mutations. We would have gotten the answer "we are sorry, but we don't know what caused Drew's death." I am so incredibly thankful for the Lord's hand in this simple decision that could drastically change the outcome of our future, both individually, as a couple and a family. We love you all!!
