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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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 Kristi Koop on December 12, 2009 at 1:14pm
What confuses me is that I thought the skipping would put the reading frame back in frame since it was out of frame. Well, Justin is in frame already so what benefit would it be? I have always thought the other therapies in the works would be what we would need.
Comment by Keith Van Houten on December 12, 2009 at 12:33pm
This is interesting that the doctor would talk about the possibility of exon skipping for either your sons - Lisa or Kristi - because in the web conference with Annemeike Russ back in October, she told me that exon skipping would likely not be effective if you're missing any of the first 8 or so and last 10 or so exons. Apparently, it's critical to have those regions intact in order to produce functional dystrophin. This is not proven at this point as I understood it, but was the current thinking. I'm particularly interested in this as well, as my son has an exon 5 deletion.

We'll be at Cincy in February, I'll ask about this front and back end thing in some more detail.
Comment by Lisa Jones on December 11, 2009 at 10:53pm
Kristi,
Dr. Rybalsky (the doctor from Russia) mentioned exon skipping but said it may be awhile before a compound is available for Bradley. She mentioned Utrophin being promising and said they may be part of the trials for utrophin. I think Dr. Wong just has too many patients to see them all. She tries to at least see the DMD patients initially. Bradley is doing good and is maintaining strength. He has stopped growing in height though. If he doesn't grow any by June, he will be in the 10th percentie for height in June. In June, we will be doing testing for HGH and Glucose Tolerance/Insulin resistance. So we are going to be thinking about HGH and Metformin (for weight control) over the next 6 months. I asked about Outliers but she said there are really three severities (mild, intermediate, severe). She said she thinks Bradley is in the intermediate group.
Comment by Kristi Koop on December 9, 2009 at 1:35pm
Hopefully you will see this before seeing Dr. Wong. Justin was in Cincy April. He saw the doctor from Russia (I think that is where she is from) and she mentioned that Justin may be able to do the exon skipping. He has deletions 3-12 and is in-frame. Being that he is in frame I did not think that exon skipping would work. Would you mind letting me know if they make mention of this at your appointments? I hope everything is good news this time as well.
Comment by Lisa Jones on November 27, 2009 at 9:16pm
This is what the exon checker said:
"Duplicating exon 2 leads to ... an OUT-OF-FRAME duplication."
Comment by Keith Van Houten on November 27, 2009 at 3:20pm
Is an exon2 duplication out of frame? The frame checker webpage doesn't work on a Mac for some reason, so I couldn't check.

There's 14 cases in the Utah database with an exon 2 duplication. 2 show a BMD phenotype, 12 show DMD. The Leiden database is online also, but it's complicated, I can't follow it. It's bigger than the Utah one. You might ask Dr. Wong to look at it for you.

Sounds like your son is doing as well as can be expected, which is great news, and what really matters in the end anyway.
Comment by Lisa Jones on November 26, 2009 at 9:37pm
Thanks Keith.

We are going to Cincinnati Children's again Dec. 9-10 so maybe we should ask Dr. Wong if this is a possibility. The DMD team does seem amazed that Bradley is doing so well. A lot of people still say he seems very normal to them....of course, these are people who aren't around him everyday. We know he is not normal because we have seen the progression of his DMD. Compared to other boys with DMD, he just seems to have a milder case.

Dr. Wong did a thigh MRI on him in June 2008 and said the deterioration looked like DMD. This test was done because even then we questioned whether he really had DMD or whether it could it be BMD instead. (His muscle biopsy in 2001 showed "only a few" revertent dystrophin fibers-but his diagnosing neurologist back then said "revertent" basically meant these fibers had no dystrophin value). Later on (2005), we had the gene test which showed the exon 2 duplication. Initially, when a gene test was done in Nov. 2000, it didn't pick up any mutations which brought us to the muscle biopsy.
Comment by Keith Van Houten on November 26, 2009 at 4:52pm
Well, you won't know for sure if your son is an outlier until his you see his progression outside of the normal range for the predicted phenotype.

You can get an indication of whether the mutation is an anomoly to the reading frame rule by looking at the duchenne registries. For example, in our case, our son has an in-frame deletion - expected BMD by the reading frame rule - but the registries show all the cases with DMD, IMD, or B/DMD. There's a paper out there on this - that's how they came up with the guideline that the reading frame rule holds 93% of the time.

Looking at the registries doesn't capture everything, though, because not every mutation has enough entries to draw any conclusion. Also, different people with the same mutations progress differently - even within the same family.

Good luck!
Comment by Lisa Jones on November 25, 2009 at 10:17pm
So how do you know whether your son is an Outlier between DMD/BMD? My son seems to have a milder case of DMD. He will be 13 in March and is still walking and getting around well. He has a duplication of exon 2.
Comment by Regina on October 4, 2009 at 10:32am
Hi Melissa-- was Dr. Finkle referring to serial casting? I have a friend whose child goes to him for another neurological disease w/very similar symptoms, and she did serial casting over last spring. She said her daughter had immediate benefit, but it was very short lived-- the heels shortened up again very quickly. Dr. Finkle mentioned it to us at our last appl. in Feb as maybe something to consider down the road. However, my friend's experience made me decide I won't do that anytime soon. Maybe much later if it is absolutely necessary to keep him getting around.

PS-- Avalon is great! We try to spend as much time in the summer as we can in OC, and I know all the walking in the waves and body surfing is great PT! My son doesn't even go to PT in the summer b/c the normal activities are sufficient.
 

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