Does anyone know which exon or exons would have to be skipped for my grandsons' mutation, which is a duplication of exons 8 thru 11? Where can I find that information?

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I'll go back through the files Cheryl and send you the information - it is still in its infancy, as they are trying to establish proof of concept, however 15 years ago exon skipping stood at the same starting block, and look where we are now :)

Hope you are keeping well,

Jules xx
cheryl cliff said:
Hi Julie,

Could you provide a bit more information as to who is doing the delivery of truncated dystrophin you mentioned?
Hi Julie: Could you send me that information too! Thank you. Terry

Julie Gilmore said:
I'll go back through the files Cheryl and send you the information - it is still in its infancy, as they are trying to establish proof of concept, however 15 years ago exon skipping stood at the same starting block, and look where we are now :)

Hope you are keeping well,

Jules xx
cheryl cliff said:
Hi Julie,

Could you provide a bit more information as to who is doing the delivery of truncated dystrophin you mentioned?
Thanks Julie!! I appreciate your help and yes, we are well. Hope you guys are doing ok.
cheryl

Dear Terry, Julie, 

I assume the disconnection is between adjuscent exons original  exon 11 and duplicate exon 8. I wish if a way been discovered to discriminte those exons.  Another option is skipping of exons 7 thru 12 reduces the severity to BMD.

 

Dear Julie,

 My sons (7y and 3y) have a deletion from 12 to 25. I assume that skipping of exon 11 will solve their problem but is anywhere such a study happening. Please advise.

Thanks and regards

Vinu

 


Julie Gilmore said:

Annemieka also reported the very duplication you are enquiring about in a recent report outlining the current situation on exon skipping:

http//www.treat-nmd.eu/userfiles/file/general/Exon%20Skipping%20Report%20...

The entire report is well worth reading as it is very informative and gives a great outline of the process involved in exon skipping. However specific to your request, page 6 reads as follows:

"At the request of a family whose son had the exons
8-11 duplicated, Annemieke answered to explain the difficulties:
“We would need a combination, a cocktail of AOs
targeting all four exons 8-11. But these AOs cannot discriminate
between the original and the duplicated exons.
So the result will be skipping of either the original exon 8,
the duplicated exon 8 or of both exons 8. Or it may skip
the original exon 9, the duplicated exon 9 or both, or a
combination of exons 8 and 9, and so on. Thus there are
many possibilities only one of which – skipping the duplicated
exons 8, 9, 10 and 11, but not the original exons 8, 9,
10 and 11 – will restore the reading frame. The effect is
diluted. Simply increasing the amount of the AOs in the
cocktail will not change the situation. We are trying to find
solutions for these problems but things are not as straightforward
as with deletions. We do not know if, and if so,
when exon skipping will be applicable for large duplications“.

I'm sorry I couldn't offer you a more encouraging answer, however this technology has come along in leaps and bounds in the last decade, and who knows where it will lead us in the future?

Hugs to you and your family,

Jules

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