Yesterday at my sons Dr. appointment we got copies of the DNA test that was done to determine his specific mutation. He was diagnosed in July, and I still feel so much in the dark and really not very smart about all of this still. I was wondering if someone would be able to help me understand exactly what his mutation was, and what if any trials he may qualify for now or in the future.

DMD Sequencing: Sequence Alteration - Predicted Positive

DNA Variant 1: Transversion T > A
Nucleotide position: 918
Codon Position: 306
Amino acid change: Tyrosine > OCH
DNA variant type: Predicted disease-associated mutation (hemizygous)

Thanks in Advance,
Kim

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Kim,
I know it's confusing and while I can't help you make sense of this (I don't see where it says anything about deletions or duplications, or where it says which gene sequences are deleted or duplicated), I just want you to know that we've all been in the beginning stages of this and I can say, that I don't ever want to be there again. Very in the dark, very difficult to figure out what is what, and where to even begin. I would call your doctor and ask, exactly if your son has deletions or duplications and what is the sequence. For instance, my son Nicolas has deletions of exons 45 through 50. It is tough to figure out exactly what this means, but it puts your son in the category of either Beckers or Duchenne. Because of my son's deletions, it was obvious that he has Duchennes. Also good to note that there is treatment out there being looked into for Exon Skipping, and they're starting with exon skipping 51, which my son qualifies for, and is on list to begin trials.
Again, I know it's all a bunch of confusing scientific and medical terms that are hard to understand, but trust me, you will understand, and you will know way more than your son's pediatrician and other specialists. Be patient with yourself.
Michelle
Hi Kim,

Like Michelle said the exon your son has a mutation on isn't clearly spelled out with the info you have. You might want to take a look at Duchenne Connect, here at PPMD website, to obtain more information. There is no charge. You can set up a phone appt to speak to one of their genetic counselors if you don't feel your doc can give you enough information (lots of them get confused with specific genetic science). Or you can contact them by e-mail. Since you do have nucleotide and codon positions Duchenne Connect should be able to tell which exon your sons mutation is on. There are 79 exons on the dystrophin (the missing protien) chain. Each exon has a certain amount of necleotides and codons, I believe, are little messingers going inbetween the exons. If the message gets changed or stops before reaching completion the body can't make enough dystrophin to repair muscle damage, as damage normally occurs daily. They can explain in much better detail than I, how all this works and where to get more info.

Exon Skipping medication is in clinical trials now for skipping exon 51 only so it helps finding out which exon you are working with. Other exons are coming up for trials later.

The science behind DMD, exon skipping and other strategies is VERY confusing, especially at the start. Plus, having such exteme emotional issues diminishes capacity to take in and retain data. If you can't find your way with D. Connect let me know and we can try something else.

cheryl
Kim. I know how hard it must be to take in all of this new information. It's going to take lots of time. Right now, the best person to talk to is your son's doctors. The results are in very technical terminology, nothing too mommy friendly about it.
I learned all the basics about DMD from Jason clinic doctors. I have very good teachers. Jason is now 24 and we are in fairly new territory with having an adult with DMD. We are learning new things every day. Our doctors are our best source. I know, not everyone has great doctors. give them a try and see what they give you.
Hi guys,
Thanks for helping me out. Tanner has no deletions or duplications, at least that is what his results say. It is simply stated as a sequence alteration. His MDA Dr. is pretty much clueless and all he could do at this appointment and his last appointment was read to me directly from the test results itself. He even told me he didn't understand parts of it, which I can understand because he is not a geneticist. All he could tell me was basically that 2 of Tanners Amino Acids swapped places and that caused the DMD. I meant to get a copy of his results in July when he was diagnosed with DMD I just simply forgot. We totally expected to have the diagnosis of DMD however it was much more overwhelming then we had initially anticipated. Now that it has been about 3 months, we have time to absorb it all a bit better and to focus on things more.
We are even considering a move to try and get a better Dr. for Tanner. We just still feel so lost. But, I do know I am not alone.
Kim
When you got the diagnosis, was there a counselor there? We had an amazing genetics counselor in the room and she explained it in terms I could understand. My son, Wyatt, has a deletion of 49 and 50. She explained it like this dystrophin is made up of chapters like in a book. Wyatt is missing chapters 49 and 50 so the "book" won't make sense. It's like reading a novel and 2 chapters being missing. My point (I ramble sometimes, sorry) you need someone "who does know (sounds like your doctor isn't sure)" to explain it to you. They owe you that much. Right now, you need to get the mutation information, that way you can find out about trials, treatments, etc. Our son was diagnosed when he was 10 months, (he's 19 months now). the 9 months has been a blur of learning new things everyday. This is a hard disease to understand fully, so don't feel bad if you "are in the dark". Your journey has just begun. I have found a lot of support on this site and I hope you do too. Good Luck. About moving, we thought about that too, but then we realized that where we live shouldn't stop us. We live in Washington State, but take Wyatt to Cincinnati Children's for his DMD related care.

Have a great night.

Melissa
Nope no counselor. Just myself, my hubby, my Mom, and the Dr.
Tanner does not have a deletion or a duplication, I am wondering if this is a nonsense mutation? Still not really sure what that means.
We would love to be able just to travel to get him better care, but we simply can't afford it. We struggle with day to day bills and traveling is out of the question, we also have 2 other children to support, . Not to mention getting insurance to cover it and getting the time off of work to be able to leave, and the co-pays would be crazy.
We live in south central Idaho and we already have to drive 2 hours just to see the Dr. in Boise, Salt Lake City is about 3 and a half hours from us. Those kinds of distances are do-able but anything beyond that is just not possible.

Wyatt's Mommy, Melissa said:
When you got the diagnosis, was there a counselor there? We had an amazing genetics counselor in the room and she explained it in terms I could understand. My son, Wyatt, has a deletion of 49 and 50. She explained it like this dystrophin is made up of chapters like in a book. Wyatt is missing chapters 49 and 50 so the "book" won't make sense. It's like reading a novel and 2 chapters being missing. My point (I ramble sometimes, sorry) you need someone "who does know (sounds like your doctor isn't sure)" to explain it to you. They owe you that much. Right now, you need to get the mutation information, that way you can find out about trials, treatments, etc. Our son was diagnosed when he was 10 months, (he's 19 months now). the 9 months has been a blur of learning new things everyday. This is a hard disease to understand fully, so don't feel bad if you "are in the dark". Your journey has just begun. I have found a lot of support on this site and I hope you do too. Good Luck. About moving, we thought about that too, but then we realized that where we live shouldn't stop us. We live in Washington State, but take Wyatt to Cincinnati Children's for his DMD related care.

Have a great night.

Melissa
Hi Kim,

This is Carrie's husband Stan. I am a human geneticist at UCLA and we have a son with DMD who is now 8 as well. THe mutation means that there is a single base mutation of T to A at the base position 918 within the amino acid sequence of the gene. This changes the codon at amino acid number 306 which is normally tyrosine (encoded by TAT) which is changed to TAA. This is a stop codon and so your son may be eligible for the PTC124 trials. This is called an Ochre mutation or OCH which is the reason that they have the ' Tyrosine>OCH ' change listed above is from . That is a confusing way to list the mutation, but this is an in frame stop codon mutation, which could benefit from readthrough. This is also called a nonsense mutation. I am sorry for your son's diagnosis. Feel free to ask any questions. what part of the country do you live in. The University of Utah is participating in the most recent PTC124 trials and Kevin Flanigan is leading that at the Utah Clinic from our last information. Stan
Hi Guys,

We are patients of Kevin Flanigans. Been seeing him at Univ of Utah for a couple of years now. He is really, really good with dmd kids however he is in the process of moving to Nationwide Childrens Hospital in Columbus, Ohio. So don't go through the hassle of trying to find him in Utah. I have been told there are other competent neuro's at Univ of Utah but I don't have names, sorry. We are sticking with Flanigan and plan to travel to Ohio instead of Utah (we are in Cal so air travel was already part of the game). I think the PTC trial there at Utah is still ongoing.

Kim, I have heard of some airlines who let you fly FREE to medical appointments. Look at Contenental for starters. Plus there are reduced rate hotels around the hospitals too if you specify medical necessity. Polly Sundeen, here at ppmd, would have loads of info on that stuff, in case you are interested. If you can't find her let me know!

Don't hesitate to ask,
cheryl



carrie said:
Hi Kim,

This is Carrie's husband Stan. I am a human geneticist at UCLA and we have a son with DMD who is now 8 as well. THe mutation means that there is a single base mutation of T to A at the base position 918 within the amino acid sequence of the gene. This changes the codon at amino acid number 306 which is normally tyrosine (encoded by TAT) which is changed to TAA. This is a stop codon and so your son may be eligible for the PTC124 trials. This is called an Ochre mutation or OCH which is the reason that they have the ' Tyrosine>OCH ' change listed above is from . That is a confusing way to list the mutation, but this is an in frame stop codon mutation, which could benefit from readthrough. This is also called a nonsense mutation. I am sorry for your son's diagnosis. Feel free to ask any questions. what part of the country do you live in. The University of Utah is participating in the most recent PTC124 trials and Kevin Flanigan is leading that at the Utah Clinic from our last information. Stan
Thanks everyone! All of your info has been so helpful and is exactly what I was looking for. I will see if I can find a Dr. in Salt Lake City for Tanner.

Thanks again,
Kim
Yes, it looks to me like stop codon or nonsensic mutation in exon 9 (I need to double check the exon number). Ataluren (PTC124) might work if approved.

Cosmin Filipescu said:
Your doctor is right, there seems to be a point mutation at nucleotide 918, there is one stop or nonsense codon at 306. Each codon is a combination of three nucleotides (306 x 3 = 918), there are four types in DNA: C, T, A, and G. The 918th nucleotide should have been T and is in fact A, therefore the RNA can not translate the information into functional aminoacids that make the dystrophin protein. The 918th nucleotide should be somewhere at the beginning of the gene.

If I happen to be right, that should be good news for you, your son should be helped by PTC124 (Ataluren), that induces a read through of the stop codon. They're in phase II trials (or III already, I believe), and it seems to be working well.

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