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There are alot of cases around exon 51 where the DNA sequencing predicts an out of frame mutation, however, the boys are showing atypical progression. So is this a site that exon skipping naturally occurs often or is it more prone to splicing errors and thus 51 itself will get spliced out or possibly a pseudo exon appears before 51. There are exon dependencies on introns that could cause an exon to be spliced out and also there are mutations that extends into the intron from 50 towards 51 that could cause a pseudo exon (a new exon) to appear out of an intron during translation that can put it back in frame. Unfortunately without a cDNA analysis one can only surmise what is going on. The point being 51 tends to be where this happens often and your son may be one of the lucky ones.
So to explain this better. If your son's mutation shows exon 50 as being deleted, it doesn't say how far into the intron this deletion occurs. If this deletion happens to trigger 51 to be spliced out during transcription into mRNA then the reading frame is restored. If there are other mutations occuring in the intron, this could cause it to look like an exon which will be spliced in during transcription (i.e. exon 50 is created now your back in frame again). This seems to be a region where adding an exon or removing an exon puts it back in frame so a mutation that may look bad in a DNA analysis may actually look better in a cDNA analysis (where they analyze the mRNA sequence).
If you are considering doing an open muscle biopsy, make sure you have enough specimen saved to do a cDNA and/or Western Blot test in case the immunostaining doesn't help much (immunostaining is the cheapest method and also not the most precise). I've been down this road. My son show signs of an MD, immunostaining shows DMD characteristics, Full blown DNA test showed no mutations, cDNA showed no mutations, Western Blot test showed normal levels of full weight dystrophin. Did all the other DNA MD tests, spent fortunes and still no dx. Now they want to do another open muscle biopsy and I'm resisting because my son's last biospy keloid.
irishgirl said:Hey - I forgot to ask if you could please explain further what you mention about the splicing - at more of a 3rd grade level? Haha! Thanks
MarcosDad said:I pray that it is Becker's. Exon 51 is such a hot spot that it could easily be spliced out even if DNA sequencing shows its existence which could explain your son's a-typical progression.
Hi,
My son Ryan also has a deletion of 48,49,50 and would be a candidate for skipping 51. He is very active and will turn 7 this July. Best of luck for your son's biopsy today. When are the trials coming to the US? We go see Dr. Wong on 27thApril. I am wondering if we should also get a needle biopsy done and get ready for the trials? Let me know how did the biopsy go for your son, and also which is the best place to get it done.
Hey Marco's Dad: I asked Dr. Leshner about having the cDNA and mRNA done and he doesn't know on any commercial lab that will do it. Won't Athena do it. Do you know where the sample can be sent - either US or beyond? Thanks,
Noreen
MarcosDad said:There are alot of cases around exon 51 where the DNA sequencing predicts an out of frame mutation, however, the boys are showing atypical progression. So is this a site that exon skipping naturally occurs often or is it more prone to splicing errors and thus 51 itself will get spliced out or possibly a pseudo exon appears before 51. There are exon dependencies on introns that could cause an exon to be spliced out and also there are mutations that extends into the intron from 50 towards 51 that could cause a pseudo exon (a new exon) to appear out of an intron during translation that can put it back in frame. Unfortunately without a cDNA analysis one can only surmise what is going on. The point being 51 tends to be where this happens often and your son may be one of the lucky ones.
So to explain this better. If your son's mutation shows exon 50 as being deleted, it doesn't say how far into the intron this deletion occurs. If this deletion happens to trigger 51 to be spliced out during transcription into mRNA then the reading frame is restored. If there are other mutations occuring in the intron, this could cause it to look like an exon which will be spliced in during transcription (i.e. exon 50 is created now your back in frame again). This seems to be a region where adding an exon or removing an exon puts it back in frame so a mutation that may look bad in a DNA analysis may actually look better in a cDNA analysis (where they analyze the mRNA sequence).
If you are considering doing an open muscle biopsy, make sure you have enough specimen saved to do a cDNA and/or Western Blot test in case the immunostaining doesn't help much (immunostaining is the cheapest method and also not the most precise). I've been down this road. My son show signs of an MD, immunostaining shows DMD characteristics, Full blown DNA test showed no mutations, cDNA showed no mutations, Western Blot test showed normal levels of full weight dystrophin. Did all the other DNA MD tests, spent fortunes and still no dx. Now they want to do another open muscle biopsy and I'm resisting because my son's last biospy keloid.
irishgirl said:Hey - I forgot to ask if you could please explain further what you mention about the splicing - at more of a 3rd grade level? Haha! Thanks
MarcosDad said:I pray that it is Becker's. Exon 51 is such a hot spot that it could easily be spliced out even if DNA sequencing shows its existence which could explain your son's a-typical progression.
Thank you so very much. The biopsy went as smooth as silk and Liam was walking around an hour after the bx was done. After doing some research, I really think the needle biopsy is not such a good idea because both procedures require anesthesia - and the needle bx doesn't give enough of a muscle sample to freeze for later. WHen the trials come - it will more likely be where we are here in DC at Children's. Dr. Hoffman is here and he is the MD king. Everything is already set up here as well. Within the next year or two they will be here, but with a higher dose of the drug. I'm very glad to know another whose son carries the same deletion as my Liam. Liam is 9.5 and very, very active. But with this trial in particular, the inclusion criteria depends on exactly how much dystrophin - or what % is being produced and the only way to tell that is with a bx. We are on excellent terns with Dr. Hoffman and he keeps us clued in on what's going on with the exon 51 skipping. We want Liam to have all of is ducks in a row prior to trial commencement. We want him ready to do. But the biopsy is necessary for ant trial of this kind. AND - it's no big deal at all!!! My son has a very low threshold to pain and is very fine. Just make sure the anesthesiologist is fully aware of the MD in your child and if he/she said you don't need to worry about that - run a mile from that doctor. Get someone who knows exactly what's going on and all will be fine!!!! Really, this was no big deal at all for your son. It will be harder on you, but I was very comfortable.
So, where are you located? Are you a regular with Dr. Wong? I hear many good things about her. How is your son? How did you find out about his MD?
And - many thanks to you for your words today!!!!!!
Noreen
Ana Vaish said:Hi,
My son Ryan also has a deletion of 48,49,50 and would be a candidate for skipping 51. He is very active and will turn 7 this July. Best of luck for your son's biopsy today. When are the trials coming to the US? We go see Dr. Wong on 27thApril. I am wondering if we should also get a needle biopsy done and get ready for the trials? Let me know how did the biopsy go for your son, and also which is the best place to get it done.
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