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I am going to switch the topic a bit for a moment if anyone wants to participate...how many of your sons would become inframe by skipping exon 51? And how many of your boys would become inframe by skipping of exon 50?
Trey has a single point deletion of 52, therefore would become inframe by exon 51 skipping...I guess you could say we are one of the lucky ones if there is such a thing with this diagnosis.
I am going to switch the topic a bit for a moment if anyone wants to participate...how many of your sons would become inframe by skipping exon 51? And how many of your boys would become inframe by skipping of exon 50?
Trey has a single point deletion of 52, therefore would become inframe by exon 51 skipping...I guess you could say we are one of the lucky ones if there is such a thing with this diagnosis.
What do you mean by "single point" deletion of 52? Does Trey have a deletion of exon 52 or point mutation in 52?
~ 13% of DMD boys need skipping 51
~ 4% of DMD boys need skipping 50
of which some might be candidates for the trials, some not, depending on trial inclusion criteria (age, ambulatory, other health conditions AND biopsy proving that the same mutation found at DNA level is found at mRNA level).
Cori said:I am going to switch the topic a bit for a moment if anyone wants to participate...how many of your sons would become inframe by skipping exon 51? And how many of your boys would become inframe by skipping of exon 50?
Trey has a single point deletion of 52, therefore would become inframe by exon 51 skipping...I guess you could say we are one of the lucky ones if there is such a thing with this diagnosis.
Good! Skipping 51 restores the reading frame.
I feel the same way, I just hope they hurry up already! Get it worked out for Trey and other kids it can help then move on to the others where really no research will need to be done since the process will already be in place... He is definitely one of the rare few who with just as the doctor referrs to it a 'single point deletion of exon 52', basically meaning he is only missing exon 52, yet I looked at his genetic results it says deletion 52, I don't know why they refer to it that way...anyhow either 51 or 53 skipping will work for him...see your son needs 50, here is to hoping and praying and wishing!
Ofelia Marin said:Good! Skipping 51 restores the reading frame.
Just an add here: Exon skipping will help boys with point mutations and duplications and some exon skips ( i.e. 45 will have a better BMD outcome (85% after skipping 45) than other skips, including 51. 45 is the 2nd most popular skip needed.
Let's just get this stuff rolling into our boys ( it's too late to think where was advocacy during all of this) and hope/pray for a positive outcome for all 65% that would benefit from exon skipping. Utrophin is another promising drug coming down the pike for all boys with Duchenne.
Most point mutations (but not all) require multiple exon skipping and the duplications cannot be restored at this point (scientists are working hard trying to make it work for duplications). As for the "better" outcomes skipping one exon vs the other, different scientist have different opinions about this at this point. I know that MDEX scientists involved in the UK trial have a different opinion than what was published in Eric Hoffman's paper showing the prevalence and possible outcomes. In fact, one can read the disclaimer in Hoffman's paper after the graph is presented as well:
“Not enough is known about dystrophin
structure and function, and the relative importance
of the protein sequence within the rod domain
remains entirely a matter of speculation. Historically, lack
of dystrophin expression has been used as the key criterion
for DMD diagnosis. This together with the presence
of theDMD clinical picture with such in-frame mutations
argues that other confounding variables such as
imprecisely defined mutation or aberrant splicing may
explain these “exceptions to the reading frame rule.” Thus,
it is anticipated that most or all patients with mutations
in the central rod domain would benefit from the production
of truncated dystrophin.”
In all fairness, only the clinical trials will prove what works and what doesn't.
Tina said:Just an add here: Exon skipping will help boys with point mutations and duplications and some exon skips ( i.e. 45 will have a better BMD outcome (85% after skipping 45) than other skips, including 51. 45 is the 2nd most popular skip needed.
Let's just get this stuff rolling into our boys ( it's too late to think where was advocacy during all of this) and hope/pray for a positive outcome for all 65% that would benefit from exon skipping. Utrophin is another promising drug coming down the pike for all boys with Duchenne.
Ofelia, do you have a link for these expamples? I'm interested in seeing them as Carter is one with an in-frame deletion that is progressing as DMD. He is missing exons 45-48. We were told that exon skipping wouldn't be of any benefit to him since he's already in-frame. Do you know if exon skipping would have the ability to help boys who are only out-of-frame at mRNA level?
Ofelia Marin said:Tina,
2. Some BMD cases progressing like DMD might have other mutations in the gene (Steve Wilton has a number of examples of in-frame mutations at DNA level progressing like DMD, proven later to actually be out-of-frame at mRNA level)
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