Hopefully someone can help! I just got my son's test results and it shows that he has a deletion of exons 45-52. Our neurologist is out until the 22nd of Sept. Does anyone know what this means? I was handed the results but no explanation. Thanks.

Views: 369

Reply to This

Replies to This Discussion

What this means is that he is missing exons 45-52 of the 79 exon gene. As far as what this means specifically for your son, that is hard to say. My son's deletions are 46-50, so we are really close to you. I can tell you that my son, who is 6.5 is doing GREAT! He has been on Deflazacort since he was 4 with very few side effects (stopped his growth, but we are now on growth hormone which is a good thing too!). Our progression seems to be pretty slow. Does that mean it will be that way for your son? Who knows! Every kid, even brothers with the same mutation progress differently.
There is an exon skipping predictor, and when I put in your deletion, it states:

The change in the DNA is c.6439-?_7660+?del
The change in the RNA is r.ex45_ex52del
The change in the Protein is p.Glu2147Ile2554LeufsX21
The Large Deletion starts in Intron 45 and ends in Intron 52.
The variant caused a frameshift of -1 nucleotide/s.
An OUT OF frame UGA (Opal) stop codon was predicted, in exon 53.
The Stop Codon is 63 nucleotides from the original variant.
It is predicted that skipping exon/s 22-44 or 53 would restore the reading frame of the gene.

The bottom line is what I feel is most important. You will see you have 2 choices for exon skipping. One may be better than the other, but one of your choices is to skip only one exon, exon 53. That will most likely happen faster than skipping the multiple exon choice.
It is an out of frame mutation, which means it is DMD and it must be put back 'in frame' to make the body 'read' it. For example:

Regular DNA: The fat cat ate the rat
Mutated (deletion DNA) in frame: The cat ate the rat (still makes sense even though fat is missing)
Mutated (deletion DNA) out of frame: Tha eth era t (8 letters missing, just like your son, the sentence no longer makes sense, so the body can't read it)

Exon skipping puts the sentence back in a readable '3 count' form. Dystrophin will be produced, butmore like the in frame option rather than the regular DNA producing a Becker rather than a Duchenne.

I hope this helps and doesn't confuse you more!!!!
Lori
My son has the same deletions, just turned 6 yesterday (Happy Birthday Kelvin) and if I didn't tell you, you'd never know anything is wrong (he doesn't realize it either most of the time). He only gets tired on occasion. Kelvin is on a lot of supplements and is on Deflazacort, all by choice, except the Calcium that he needs due to his bone density being lower. His doctors have all said that typically this is a deletion that progresses more slowly and that he may remain strong for a very long time and that he could be more of a Becker MD child. We don't know, as we haven't and probably won't do the muscle biopsy unless necessary or if he would be in a clinical trial. Keep in touch please, as there are a few kids on here with the same deletion. Michelle
Hi Kelvinsmom - how did you find out details on your sons deletion? I have asked and asked if anyone has figured out how to predict progression of the disease based on which exons are deleted and I haven't been able to get any answers. I would love to hear the same news you have about your son.

Thank you,
Jaime - KarstensMom :)

Kelvinsmom - Michelle said:
My son has the same deletions, just turned 6 yesterday (Happy Birthday Kelvin) and if I didn't tell you, you'd never know anything is wrong (he doesn't realize it either most of the time). He only gets tired on occasion. Kelvin is on a lot of supplements and is on Deflazacort, all by choice, except the Calcium that he needs due to his bone density being lower. His doctors have all said that typically this is a deletion that progresses more slowly and that he may remain strong for a very long time and that he could be more of a Becker MD child. We don't know, as we haven't and probably won't do the muscle biopsy unless necessary or if he would be in a clinical trial. Keep in touch please, as there are a few kids on here with the same deletion. Michelle
Hi Jaime
The way to find out your son's specific mutation is to have his gene sequenced. There are several labs that are doing research on dmd and need subjects with specific mutations. The University of Utah (Dr. Flannigan's group) has created a subject bank of subject with dmd and bmd. They sequenced my son's gene for the cost of overnight delivery of a blood sample. I think it is important information to have.
Karen (son Erik16)
Actually, Kelvin's doctors (at 2 different hospitals) have commented on his progression due to his specific deletions. There have been quite a few children with Becker with Kelvin's deletions, even though he is out of frame. I had a doctor tell us a few weeks ago that Kelvin may be strong for a very long time (he is very strong on his measurements and the doctor said I am doing everything right! Boy, that felt good, but I wouldn't be doing what I'm doing without PPMD!!!!). They are basing it on his specific deletions and his progression (strength, symptoms, tests, etc.) at this point. Of course, without a muscle biopsy, we won't know for a long time if Kelvin is Becker or Duchenne (of course, Duchenne is the diagnosis at the current time because of his deletion and being out of frame). Dr. Mendell explained at a meeting recently, that there is actually spontaneous exon skipping in some children (and he said they can actually produce some Dystrophin), especially those who may be Duchenne and then up as Becker. This is due to the rest of their genetic makeup, so many kids with the same deletion, can of course, end up with a very different progression. There are averages though, and because of where Kelvin's deletion is, they say he "should be" better off for awhile. What we are doing for Kelvin is written up on our main page. The doctor told us the other day that it is much better to actually get some exercise to keep the heart strong and some kids are kept from it. Kelvin plays limited soccer, swims, etc. We are busy right now putting a huge hot tub, so he can get massage and swim in it. (It is turning fall here and it is getting too cold for the pool). Sorry to ramble on so much. Michelle

KarstensMom said:
Hi Kelvinsmom - how did you find out details on your sons deletion? I have asked and asked if anyone has figured out how to predict progression of the disease based on which exons are deleted and I haven't been able to get any answers. I would love to hear the same news you have about your son.

Thank you,
Jaime - KarstensMom :)

Kelvinsmom - Michelle said:
My son has the same deletions, just turned 6 yesterday (Happy Birthday Kelvin) and if I didn't tell you, you'd never know anything is wrong (he doesn't realize it either most of the time). He only gets tired on occasion. Kelvin is on a lot of supplements and is on Deflazacort, all by choice, except the Calcium that he needs due to his bone density being lower. His doctors have all said that typically this is a deletion that progresses more slowly and that he may remain strong for a very long time and that he could be more of a Becker MD child. We don't know, as we haven't and probably won't do the muscle biopsy unless necessary or if he would be in a clinical trial. Keep in touch please, as there are a few kids on here with the same deletion. Michelle
Hi!! Did you ever meet with your doctor regarding your son's deletions? You probably already know this now, but this explanation help me a great deal with understanding my son's deletions. My son is missing 48, 49 and 50. He will be nine in a month and we just found out he's got MD this last June 12th. O.K. - there are 79 exons on the strand of DNA and they all fit together like a puzzle. If a piece or pieces are missing, the puzzle cannot be finished. In my son's case, exon 47 doesn't fit into exon 51. Exon 47 does, however, fit perfectly into exon 52. Therefore, with this new AVI stuff, exon 51 can be skipped and then 47 slides right in place next to 52 and the strand is hence completed. Dr. Eric Hoffman, the pioneer of MD, told me last Wednesday to avoid Prosenca or the studies going on in the Netherlands as they are using an older drug that is doing absolutely nothing. In London, Hammersmith, they are about to begin Phase 2 studies with higher doses of an AVI drug. At Children's Hospital in DC, where Hoffman resides, once the drug dosage is set higher without toxicity, trials will begin within the year here in the US. The FDA send Hoffman a letter asking him to provide a report where this exon skipping had worked in mdx mice. Well, he's completed those trials already and it would appear that the FDA will not hold this up at all. Also, there is quite a bit of $$ in these impending trials.
Our problem is this: our son will be nine in a month and is very strong. He is taking Deflazacort and it is helping only in very tiny ways. Prior to starting the drug last July, our son ran, jumped, swam and did all sorts of things that he still does today. Hoffman is a little concerned that Liam may be naturally doing some exon skipping of his own - and that would make him unable to partake in this trial. Good news - it would mean our son has Becker MD. So either way, I have hope unlike before. Dr. Hoffman ended our meeting with the statement that boys with DMD who are nine do not run. They may walk still, but they don't run. Liam runs, Liam jumps, Liam rides horses, Liam hikes, Liam goes up and down stairs, Liam doesn't toe walk and really showed no symptoms of this disease until age 8 - and he runs a bit slower than his classmates, and he used gower sign to get up most of the time. Other than that - nothing. Exon skipping is coming and when it does, it sure will be something.
I forgot, I looked it up and Exon 44 will fit into exon 54. It won't fit into 53, but if and when they can skip this many exons, your boy could be golden. I just have to hold on to that hope. Here is an excellent site for the scientific background of the exon skipping therapy that is written for non-medical people like me. CHeck out www.humgen.nl/lab-aartsma-rus/

Reply to Discussion

RSS

Need help using this community site? Visit Ning's Help Page.

Members

Events

© 2019   Created by PPMD.   Powered by

Badges  |  Report an Issue  |  Privacy Policy  |  Terms of Service