Very Exciting Email!

Yesterday I received a wonderful email.  It was from a man named Professor Yanick Crow, who is from England.  He mentioned that he had seen my post on the AGS website and wanted to offer some possible help with the questions that we have.  Well, I looked him up here  http://www.manchester.ac.uk/research/Yanick.crow and after reading a bit about him, knew this is who we need to be in contact with.  I wrote back to him and said that yes, we would be very interested in having Dr. Narayanan get in touch with him to discuss our situation.  I emailed Dr. Narayanan about being in touch with Dr. Crow and he said,"This is absolutely great.  Dr. Crow is of course the leader in this field."  He said to go ahead and pass his email address on to him and sent a little write-up on where we are at as of now.  I'll add it here since it helps clarify things just a little bit.
Right now we have found one sequence variant in the SAMHD1 gene in both Bryce and Annalise (Dr.Hyland thinks this is a mutation rather than a benign variant).  It looks like they both inherited this mutation from their father.

The presumption is that, in order for them to have AGS, they would have to have a different mutation in the other copy of the SAMHD1 gene that they inherited from you.  This has to be something that is not able to be detected by the sequencing method used in Dr. Hyland’s lab.  There are certain types of mutations (especially deletions of large chunks or even the entire gene) that could be missed by traditional sequencing.  Which is why I thought that we should try to devise methods for searching for another mutation in Bryce and Annalise.

If Dr. Crow is able to do this type of testing (MLPA test), or if he has other ideas, then we can easily send him some DNA from Bryce and Annalise (and you and dad too).

So, I emailed this information to Dr. Crow and within a couple of hours I had a response saying that he had replied to Dr. Narayanan.  That was just before 10:00 last night.  I woke up at 6:00 this morning and saw that Dr. Narayanan had already sent me a message saying that he and Dr. Crow had already exchanged a couple of messages and that he was going to send Dr. Crow the DNA sequence information today and then he (Dr. Crow) would decide if he is able to test the DNA samples to locate another mutation (deletion).  I guess that he has a kit to look for deletions in SAMHD1, from a company in Europe, that won't be released to the general public commercially until December.  Can you believe that?!   How awesome is all of this that has taken place in less than 24 hours.  So, Dr. Narayanan asked if it would be OK for him to sent the DNA to him.  I of course wrote back and said that YES, it would be fine.  Now I will wait until I hear what is happening.  We are so excited that Dr. Crow took the time to contact us and we hope that he will be able to help us discover the missing gene.  

I have also been in contact briefly with 3 families who have children with AGS.  2 of which are actually here in Arizona.  It's amazing.  Please keep the prayers coming.  They are most certainly helping us to be in touch with those who we need to be!

Happy Birthday Annalise!

Yesterday our Princess Annalise turned 2 !

Singing Happy Birthday.

Looking at her new doll.

Bryce and Annalise both enjoy the talking Dora Backpack.

What a sweet, wonderful daughter we have.  I think she enjoyed her special day!  

Benefit Concert

The benefit concert tonight went really well!  Thank you so much to Will Perkins and to everyone who helped make this so successful.  What a fun night!

More Answers which lead to More Questions

Ok, so more answers, more questions.  I heard from Dr. Narayanan today about the DNA results from the latest tests.  Bryce tested positive for the same mutated gene as they found in Annalise.  Ok, so it looks like it is AGS.  So then they tested my blood for the same gene...negative, I do not carry that mutated gene.  Tested John, positive... he does carry the mutated gene.  So...yes something is going on, but what.  Dr. Narayanan believes we are on the right track, but it just doesn't make sense to any of us.  If it truly is AGS5, that is causing this regression in Bryce and Annalise, they must have 2 mutated genes...it's an autosomal recessive disorder!  So where is the other one?  He said that if they can find the other mutated gene in one of the kids, then they could test me for that and probably make a connection.  But so far, nothing else is showing up.

The really odd thing to think is that this still could mean that John, Bryce, and Annalise are all just carriers of AGS and what they "have" is something totally different!  Honestly I doubt it , but who knows.  Although ,as odd and unrealistic as that seems, that actually is what would make the most sense when strictly looking at the results that we have found.  AUGH!  It's totally mind boggling.  Dr. Narayanan said that he isn't sure what the next move should be.  He is going to think on it for a couple of days, talk to others in the team, and get back to us.  All I know is that something strange is going on with my kiddos and I would really love to find out what it is.

Approved!

I got the phone call this morning...Annalise was approved for long term care!  We are so excited and thankful.  Prayers are being answered.

A Mutated Gene Has Been Found!

Good news, bad news?  I'm not quite sure.  There are still many unanswered questions, but at least we finally have a definite step to follow and research.  OK, bear with me, this is a little difficult to explain (this goes way beyond what I ever learned in Biology!), but I will do the best that I can.  When we saw Dr. Narayanan  last Wednesday afternoon I got some very interesting information.  As of that morning, only 4 of the 5 gene tests for AGS had come back...all of which were negative.  So before we got up there, Dr. Narayanan got a hold of the person who was doing the gene testing and asked if he had the final results.  He said that he did, but they were a little confusing.  What he found was one mutation on the least common of all the AGS causing gene symbols (SAMHD1).

Now, the strange part about that is that AGS is an autosomal recessive disorder, meaning that in order for a person to develop the disorder he/she must receive a mutated gene from each parent.  Two total.  In Anna's case, only one was found which normally would be a sign that she is a carrier.  However, if she was just a carrier, she would not have any of the symptoms...which obviously is not the case.  So, where is the other mutated gene?  Well, Dr. Narayanan explained that one of two things could be going on here.  1)  She is just a carrier of this particular disorder and what she and Bryce actually have is still something totally different than what we have found, or 2) There is a deletion of a gene.  Now, as far as I understand it, this means that there is a gene (or exome, maybe?) that is completely missing.  The trouble is that these deletions do not show up in genetic sequencing and there is currently no clinical test to determine if there is a deleted gene.  Dr. Narayanan said that this may be his next move...to find a way to determine if there is a deleted gene and what it is.

So, where do we go from here.  Well, we signed some forms and sent them to the gene sequencing person (sorry, I don't know what he is called) and Dr. N sent off the blood he has stored for Bryce, John, and I.  They will first test Bryce to see if he has this same gene mutation.  If not, we will figure that Annalise is a carrier of AGS and we will continue on our search. They will also test John and I to see which of us is the carrier.  If Bryce does have the mutated gene, they will test John and I to see where that particular gene is coming from, and go from there.  Hopefully we will have the results in 3-4 weeks. Until that time, I will try to keep from going crazy with the what-ifs of it all.  My brain has been spinning since Wed.  Luckily we keep very busy these days so time should go quickly.  Then we can deal with whatever is found.  I will definitely keep you posted!

Evaluation Results

The evaluation went well although initially Annalise does not qualify for long term care.  However the lady doing the evaluation was able to see that ours is a unique situation and that although Annalise does not fit into the state's normal criteria of a child in need (which is so frustrating!), she will indeed need long term medical assistance.  So, she is going to go ahead and pass the paperwork on up the chain with a long description of what Bryce has been through and where he is now and where Annalise is heading.  I gave her the notes I have from the neurologist and faxed the rest that I could get a hold of.  I also faxed a description of Leukodystrophy from the ULF website since most people don't know much about it.  She said that if worse comes to worst and Annalise is denied, we can apply for long term care again.  I know that is possible, and exactly what I would do, but I really hope we don't have to go through that again.  Bryce wasn't approved until the second time around and it is just a waste of everybody's time and money, not to mention, emotionally draining.  Anyway, I guess we will know in 2-3 weeks if she qualifies or if we start the process all over again!