Outliers - Intermediate between Duchenne & Becker MD

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Outliers - Intermediate between Duchenne & Becker MD

The reading frame rule holds true 90% of the time. There remains those 10% that does not fit dmd/bmd phenotype. There is a 3rd form that may be considered as an intermediate between Duchenne and Becker MD(mild DMD or severe BMD.

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Latest Activity: Dec 10, 2018

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Outliers?

Started by Simone & Elias. Last reply by KarstensMom Dec 31, 2017. 16 Replies

Utrophin

Started by Eliane Khoury. Last reply by Keith Van Houten Mar 25, 2009. 1 Reply

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Comment by Char Burke on March 14, 2009 at 7:29pm
Thanks Keith. You didn't meet me in D.C. last month. We made our trip to see Dr. Wong in early Feb. and that was about it. I would like to go to that event some day. I have been to one PPMD conference and really enjoyed it albeit it was very intense with knowledge. Thanks again for your insight. Char Burke
Comment by Keith Van Houten on March 14, 2009 at 6:38pm
Char, when the deletion is out of frame - that's when exon skipping would apply. The skipping restores the reading frame - making the deletion now larger, but in-frame. Honestly, I'm not sure how duplications effect the reading frame, and how exon skipping would work. If you have an in-frame deletion, exon skipping would theoretically not help. Something different than expected is happening with boys with in-frame deletions and DMD like symptoms, though, so perhaps someday they'll look at this as an option.

Did your son's DNA test work indicate a phenotype? If I follow your posts correctly, it sounds like it said BMD.

On the DMD/BMD diagnosis thing - I don't think it has anything to do with funds. Projected phenotypes come from the reading frame rule. One study showed that when you compare that rule to the registries of how patients actually progressed - it held in 93% of the cases. The 7% that didn't conform to the rule are the so-called "anomolies". Some of these anomolies are grouped up around particular mutations.

Based on the 3 clinics we visited, most doctors choose an initial course of treatment based on the reading frame rule, and don't consider the patient might be in the other 7%. This was the case with us, even when I pointed out to one doctor the anomolies, and that my son's mutation was specifically written about in the literature as an anomoly and had a DMD phenotype in the registries. Dr. Wong recognized all of this on visit number 1 and put him on steroids and night splints immediately.

On the range of BMD thing - I suspect the geneticist meant it was "in the range" of BMD because it's an in-frame mutation. Not particularly well worded. You can definitely have BMD with a mutation anywhere in the gene. There may be places it's more common - just like there's a common area for DMD, but can occur anywhere in the gene. Similarly, there's probably regions that are more common for duplications, as you mentioned.

Did I meet you in DC last month?
Comment by Char Burke on March 14, 2009 at 11:38am
So - Keith - when the reading frame is in frame, I know that exon skipping would restore the error....but does it also mean that it is less severe than the out of frame error from a disease standpoint. Char
Comment by Char Burke on March 14, 2009 at 11:36am
Keith - One of the parents on this site - listed that he had heard that most boys are diagnosed with DMD b/c when it's DMD, more funds are granted vs. BMD. If you look at the BMD group site, you will see this.
Actually, I see the DMD vs. BMD on a huge spectrum...I know several BMD men who were in a wheel chair in 10 yrs range and don't have upper body use but just don't have the cardiac involvement that DMD men do. Char
Comment by Char Burke on March 14, 2009 at 11:31am
Keith - When Will had the DNA duplication test done at Baylor, the geneticist there said that the duplication was in the range of BMD....I tried and tried to get ahold of the geneticist but he wouldn't talk to me. He recommended a muscle biopsy. That incident lead me to believe that there is an area of the gene - in the 40's that is commonly associated with BMD. Actually, there are, I was told, about 5 areas of the gene where there are popular for duplications. One area is the beginning of the gene, another area is in the 40's ....can't recall the rest. Char
Comment by Keith Van Houten on March 14, 2009 at 11:04am
By the way, our situation is the similar to Rhiannon and Char. DNA results are in-frame, but Dr. Wong says his clinical presentation is consistent with DMD, and the registries list almost all the cases as DMD.

He started on Prednisone in January.
Comment by Keith Van Houten on March 14, 2009 at 10:54am
The easiest tool to look at in or out of frame is this one: http://www.dmdregistry.org/reports/predictor/

When you mention a "BMD zone" - are you asking what the most common mutations are for BMD? That I have not seen. I've seen it for DMD, and I think it's an exon 50 deletion, which is why exon skipping research focused on skipping 51, which restores the reading frame for a exon 50 deletion.

I have seen people discuss that BMD with deletions in the 50's somewhere (can't recall exactly) is linked with earlier heart complications.
Comment by Char Burke on March 14, 2009 at 12:44am
Dr. Wong has diagnosed Will with DMD due to his clinical presentations. We have not had a muscle biopsy but we have had dna tests done at Baylor and participated in Dr. Flannigan's clinical study.
Question - does any one know where the BMD zone area is in the dystrophin gene? I have heard it's in the area of the 40's through to the 50's. Thanks. Char
Comment by Char Burke on March 14, 2009 at 12:41am
So, our son has a duplication of exons 54-57 and if I can rely on the Leiden data base, then his mutation is in frame. Have others used the Leiden tool to determine in or out of frame?
Also - Keith - have you read the article that Dr. Flannigan published about mutations early in the exons being more mild? Char Burke
Comment by Keith Van Houten on March 11, 2009 at 6:56pm
Rhiannon - very interesting. I'm pretty sure Mayo does their own sequencing. Your first test - "Mayo" - is that a test you had done at the Mayo Clinic, or is that the lab name, or both? I'm interested in what lab did the test.

Roxanne - what lab did your DNA test, what mutation did they list, and how did it list the phenotype?
 

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