Does anyone here have a boy or know of a boy that has deletion of exons 3-12?

My sons have deletion of exons 3-12 althought it should classify as beckers because it is inframe my older son is still diagnosed with duchenne because of his severe symptoms at such a young age and the fact that after a muscle biopsy they thought he had duchenne rather then beckers and that just means that the dystrophin level in his muscles is very low.

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Hi Sif,

Our Son is missing exxons 2-21. We visited Dr. Kevin Flanigan at Nationwide Children's Hospital in Ohio to get some of the same answers. What he told us that we did not know, is that Essons work in groups of 3. To demonstrat this, he wrote a sentance on the white board in his office using 3 letter words. "The big red dog ran and got the bal." In our son's case, if we line up his delition with the sentance, in lamens terms, his body doesn't even know that there is a dog, no less that it is big, or red. Also, the first few exxons in the gene are what litarally turn the gene on. I'm not sure, but I thing the "in frame" thing only really benefits those with deletions later in the gene, in the 50's maybee.

Our Son is 5 years old, and has been on Prednizone for about 3 months. I would encourage you to take a look at the following webinar www.parentprojectmd.org/site/DocServer/7-7-11-Peay.pdf?docID=11608 .  I found it very helpfull. The steroids have helped our son have more energy in general throughout the day, so that he can attend full day kindergarden. He already has a manual wheelchair, and uses it throughout the day, so that he does not get to tired.

I hope this is somewhat helpfull.

In-frame deletions resulting in becker and out-of-frame deletions resulting in duchenne, otherwise known as the reading frame rule, is not a guarantee.  It's a "rule of thumb" - that is, it's generally true, but not always.  There are exceptions, typically referred to as "outliers".  A study was done years ago looking at patients' genotype, which is what the DNA would predict, versus their phenotype, which is how they actually progressed clinically.  That study found the reading frame rule to hold true in about 91% of cases.  I probably have the paper on my hard drive somewhere if you want to read it.

 

Some mutations are frequently found to be outliers - often times they involve the early part of the dystrophin gene, which is known as the actin binding zone, and is particularly important to how the protein interacts with muscle tissue.  Sometimes, differences between genotype and phenotype can be traced to differences between the DNA and the transcript, or the RNA.  Other genetic modifers can impact this as well, much of which is not understood at this point. 

 

Muscle biopsy is the gold standard on determining phenotype.  The absence of dystrophin in a biopsy is duchenne.  If your son has very low dystrophin levels, with severe symptoms at a young age - he has duchenne, regardless of the genotype of his mutation.

 

My son is in-frame and has dystrophin in his biopsy, but is progressing in some aspects on more of a duchenne path than a becker path.  The doctors call it "intermediate MD".

 

There's a group on this board called something like "outliers" - who have similar cases to yours and mine where there's a mismatch between genotype and phenotype.  There's some further discussion on the subject there.  Check it out. 

 

Good luck,  Keith

I would love to read the paper if you still have it somewhere! I will send you a message with my email.

I haven´t found that group.. but maybe i am just bad at searching will search better tonight! Thank you so much for your reply it helps a LOT"

Keith Van Houten said:

In-frame deletions resulting in becker and out-of-frame deletions resulting in duchenne, otherwise known as the reading frame rule, is not a guarantee.  It's a "rule of thumb" - that is, it's generally true, but not always.  There are exceptions, typically referred to as "outliers".  A study was done years ago looking at patient's genotype, which is what the DNA would predict, versus their phenotype, which is how they actually progressed clinically.  That study found the reading frame rule to hold true in about 91% of cases.  I probably have the paper on my hard drive somewhere if you want to read it.

 

Some mutations are frequently found to be outliers - often times they involve the early part of the dystrophin gene, which is known as the actin binding zone, and is particularly important to how the protein interacts with muscle tissue.  Sometimes, differences between genotype and phenotype can be traced to differences between the DNA and the transcript, or the RNA.  Other genetic modifers can impact this as well, much of which is not understood at this point. 

 

Muscle biopsy is the gold standard on determining phenotype.  The absence of dystrophin in a biopsy is duchenne.  If you son has very low dystrophin levels, with severe symptoms at a young age - he has duchenne, regardless of the genotype of his mutation.

 

My son is in-frame and has dystrophin in his biopsy, but is progressing in some aspects on more of a duchenne path than a becker path.  The doctors call it "intermediate MD".

 

There's a group on this board called something like "outliers" - who have similar cases to yours and mine where there's a mismatch between genotype and phenotype.  There's some further discussion on the subject there.  Check it out. 

 

Good luck,  Keith

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