Keith, we asked both. Our local Neurologist (who says he asked Dr. Flanigan about the subject) and then most recently the genetics Dr. from UCI.
Does anyone know what future therapies will help these 10% of boys???
my son's deletion is in-frame 45-47. I'm also very excited about Utrophin Upregulation. Since Utrophin is in the body in low amounts I don't think there will be any problems with attacks from our boys immune systems. This excits me!
When we talk about in-frame or out-of-frame deletions, we're talking about how the mutation has disrupted the dna sequence. This is a complicated subject, and I'm by no means an expert.
To oversimplfy things, you can think of the DNA as a string of 3 letter words.
THE CAT ATE THE RAT
The DNA is "read" as cells are created in sequences of three. An out of frame deletion would disrupt the reading sequence. For example, if the deletion took out the T from CAT. The DNA would be read like this:
THE CAA TET HER AT
The result is a totally jumbled sequence, and the "recipe" for making the protein is lost.
By contrast, an in frame deletion takes out part of the DNA sequence such that it still makes "some" sense. For example, if the deletion took out ATE, you'd get
THE CAT THE RAT.
Here, there's still some resemblence to the original intent. You would get some type of protein created, although it might not be quite correct, or you might not get as much.
This general concept is referred to as the "reading frame rule". You can google it and find more, and better, explanations than this.
An exon 45 deletion is out of frame. There's a predictor to determine that at this website: http://www.dmdregistry.org/reports/predictor/
Hi,you said an exon 45 deletion is out of frame,but what I have in the result , my son have an in frame shift,wich is consistent with dmd. is that different from what you saying or what? I appreciate your answer.
I think you're mixing up some of the terms. This is understandable, this is a complicated subject, it takes time to soak this all in.
You said "what you have in the result". You mean from the doctor, or from the trialserve predictor? Here's what you should get from trialserve for an exon 45 deletion:
The Large Deletion starts in Intron 45 and ends in Intron 45.
The variant caused a frameshift of -2 nucleotide/s.
An OUT OF frame UGA (Opal) stop codon was predicted, in exon 46.
So, it's an out of frame deletion. When you see the term "frameshift", what they're basically talking about is whether the reading frame is disrupted. An out of frame deletion results in a frameshift.
In the majority of cases, an out of frame deletion is associated with DMD. An in frame deletion is associated with BMD. There are exceptions, though. It's a rule of thumb.
If you have a different result from a doctor, go with that. This trialserve tool is only a predictor, from what I understand.
Again, take my information - and for that matter anybody's that you get on this board, or anywhere else on the internet, with a grain of salt.