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We are about to have our 4 1/2 year old son, Beau, tested for autism. We are pretty confident that he will not be classical autistic, but he has some qualities of autism. I know that he could still fall on the autistic spectrum (maybe PDD-NOS). We deal with behavior and social issues. Is there anyone out there that is in the same boat and can give me advice on this? Help!!

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This link is also on the Tactile page, but I thought I would paste it here for ease of access:


http://www.parentprojectmd.org/site/DocServer/PPMD2007Poysky.pdf?do...


This is a great presentation outlining the full gamut of neurological disorders with increased incidence in DMD.

Hope that helps,

Jules

My question is then, does the child have to be missing all of 45 - 52 or a combination that fits into those numbers?. My son is missing 49 and 50. How does that effect him. I asked Dr. Wong about this subject because our 13 year old who doesn't have DMD is on the Austism Spectrum and she told me because we have a family history there is a SMALL possiblity, but she never mentioned this 2006 summary. (She may not no about it of course, but I got the sense it's not anything to really be concerned about. Obviously the DMD is such a bigger issue than Autism.)

Julie Gilmore said:

Hi Emily, if your son has a deletion from 45 to 52 he will still produce no Dp140 if the current indications are correct, due to the fact he has an out of frame deletion, and loss of the initiation codon in exon 51..... the mutation shouldn't affect production of Dp116 or Dp71, but it will affect all 5 isoforms upstream from the mutation....

I have included an extract of a summary presented in 2006 on the neurological function and associated deficits, and will send Dr D'Angelo an email. If she agrees, I will post the full paper up under the Tactile Sensitivities discussion group :) for those that are unable to access it free of charge via Google.........

Extract of Dr Maria D'Angelo's paper titled "Cognitive impairment in the neuromuscular disorders"; Muscle Nerve 34: 16-33, 2006

"Rearrangements in the second part of the dsytrophin gene tend to be more commonly associated with cognitive impairment as well as loss of the Dp140........ Point mutations in the Dp71 coding region is one of the most frequent findings in retarded DMD patients.

The two dystrophic mutant mice are considered to be models of DMD: the mdx mouse is deficient in full-length dystrophin in both muscle and brain; and the mdx3cx mouse lacks all the dystrophin-gene products, including the C-terminal short products normally expressed in the brain (Dp71, Dp140). The deficiency of the full length dystrophin induces specific and moderate learning and memory deficits, characterised by slower procedural learning and impaired long-term consolidation in nonspatial learning tasks and deficits in the consolidation or expression of long-term recognition mermory, but no deficits in behavioral exploration of novel objects, in the encoding of a new experience, or in short-term memory of objects. Although mild impairment of procedural learning may be a common alteration in the mdx and mdx3cv mutants, the latter shows weaker learning impairments and no overt electrophysiological alteration. Therefore, the neurocognitive evaluations in these mouse models do not reflect what is observed in humans"

J's mom said:
Hi Julie,
I am very interested in what you said about the isoform of dystrophin. My son has a deletion of exons 45 through 52. Is it just exons 44 through 51 that have this, or could my son be affected by this too? Are the neurological problems you're referring to behavior related? We have always struggled with Jake's behavior, but have never had any formal testing. Thanks!
Emily
Hi Melissa,

There are so many papers on neurological findings that I am not surprised Dr Wong did not mention it - especially given a lot of the biochemical effects of dystrophin deficiency/neurological involvement are still largely unchartered territory. (A lot of the work can only be done on biopsies of neural tissue, so it obviously is a lot harder to evaluate the role of dystrophin in the brain, as human neural tissue is not something that is readily available)

On the information given your son would have an out of frame deletion, requiring skipping of exon 51 to restore the reading frame.... given the location of his mutation, he should not be producing Dp140 if all current research is correct (based on the findings that the initiation codon is in exon 51, and you are out of frame from 47 onwards.....) therefore even though your son has the promoter site (where the RNAP binds to create the mRNA)transcription will be halted when it hits the nonsense region at 48/51. Therefore there is no initiation codon and no translation of Dp140.

Keep in mind that when it comes to neurological conditions associated with DMD, they are similar to the muscle progression in that there is a broad spectrum (as shown in the presention link I put up) and even boys with the same mutation will not necessarily exhibit the same neurological involvement. A lot of this is due to the altered pathways created during neurogenesis (no two pathways are the same when there is a deficient protein), and the subsequent effect this has on our boys. Also Dp140 is but one of the 7 isoforms of dystrophin sequestered in brain tissue, and there are a lot of factors affecting the expression of these proteins - even in boys with nonsense mutations.

Therefore the "source" of the neurological involvement is not easily defined, and could even come down to interactions with other proteins as well. Utrophin does has counter parts to the shorter isoforms, but again how this affects neural function is not yet fully understood.

The most important thing is to recognise the end result of dystrophin deficiency, and what this means to each child's neurological function, and develop strategies to compensate for any changes in the neural processes. We have been doing this with our son for 4 years, and whilst there have been challenges along the way, the benefits and improvements in his overall demeanour and school grade are immense.

Hope that helps :)

Wyatt's Mommy, Melissa said:
My question is then, does the child have to be missing all of 45 - 52 or a combination that fits into those numbers?. My son is missing 49 and 50. How does that effect him. I asked Dr. Wong about this subject because our 13 year old who doesn't have DMD is on the Austism Spectrum and she told me because we have a family history there is a SMALL possiblity, but she never mentioned this 2006 summary. (She may not no about it of course, but I got the sense it's not anything to really be concerned about. Obviously the DMD is such a bigger issue than Autism.)
Hi Miss Emily,

I am posting here, with my son having a very mild learning deficiency and a potential behavioral issue in which we believe might be very mild OCD... The poor kid is compulsive with his emotions as well as has to have everything in it's 'spot' and ALWAYS has to have something in his hands, even while sleeping. We have been blessed with great insurance so we have been able to see a myriad of doctors, but I know many have not and what we need for our boys is many times hard to come by.

Anyhow, I do know that MANY insurance companies will not pay for psychologist/psychiatric help, but WILL pay for a Developmental Behavioral Pediatrician. I never even knew these doctors existed, but they do and they can do a full medical/developmental/psychological assessment on your Beau to see if they can give you proper direction.

Many times insurance will pay for this just as they pay for a pediatrician. Just a thought...I hope you get the help you need!

Many Hugs,Cori
Of course there are so many variables, I understand that, Dr. Wong telling me there was a possiblity was enough for me to pay attention. Thankfully I know what to look for so if we have to cross that bridge we will. Your information was very helpful thank you.

Julie Gilmore said:
Hi Melissa,

There are so many papers on neurological findings that I am not surprised Dr Wong did not mention it - especially given a lot of the biochemical effects of dystrophin deficiency/neurological involvement are still largely unchartered territory. (A lot of the work can only be done on biopsies of neural tissue, so it obviously is a lot harder to evaluate the role of dystrophin in the brain, as human neural tissue is not something that is readily available)

On the information given your son would have an out of frame deletion, requiring skipping of exon 51 to restore the reading frame.... given the location of his mutation, he should not be producing Dp140 if all current research is correct (based on the findings that the initiation codon is in exon 51, and you are out of frame from 47 onwards.....) therefore even though your son has the promoter site (where the RNAP binds to create the mRNA)transcription will be halted when it hits the nonsense region at 48/51. Therefore there is no initiation codon and no translation of Dp140.

Keep in mind that when it comes to neurological conditions associated with DMD, they are similar to the muscle progression in that there is a broad spectrum (as shown in the presention link I put up) and even boys with the same mutation will not necessarily exhibit the same neurological involvement. A lot of this is due to the altered pathways created during neurogenesis (no two pathways are the same when there is a deficient protein), and the subsequent effect this has on our boys. Also Dp140 is but one of the 7 isoforms of dystrophin sequestered in brain tissue, and there are a lot of factors affecting the expression of these proteins - even in boys with nonsense mutations.

Therefore the "source" of the neurological involvement is not easily defined, and could even come down to interactions with other proteins as well. Utrophin does has counter parts to the shorter isoforms, but again how this affects neural function is not yet fully understood.

The most important thing is to recognise the end result of dystrophin deficiency, and what this means to each child's neurological function, and develop strategies to compensate for any changes in the neural processes. We have been doing this with our son for 4 years, and whilst there have been challenges along the way, the benefits and improvements in his overall demeanour and school grade are immense.

Hope that helps :)

Wyatt's Mommy, Melissa said:
My question is then, does the child have to be missing all of 45 - 52 or a combination that fits into those numbers?. My son is missing 49 and 50. How does that effect him. I asked Dr. Wong about this subject because our 13 year old who doesn't have DMD is on the Austism Spectrum and she told me because we have a family history there is a SMALL possiblity, but she never mentioned this 2006 summary. (She may not no about it of course, but I got the sense it's not anything to really be concerned about. Obviously the DMD is such a bigger issue than Autism.)
One thing I would like to mention is that NOT all the boys with deletions in that region (not producing Dp140) have learning disabilities and/or fall on the autism spectrum. I do know several boys with deletions involving hinge 3 w/o learning disabilities or autism. I assume that is the reason why doctors monitor each child individually w/o making assumptions about the location of the mutation and cognitive problems (except MAYBE for mutations close to the end of the gene where Dp71 is not produced).

Wyatt's Mommy, Melissa said:
Of course there are so many variables, I understand that, Dr. Wong telling me there was a possiblity was enough for me to pay attention. Thankfully I know what to look for so if we have to cross that bridge we will. Your information was very helpful thank you.

Julie Gilmore said:
Hi Melissa,

There are so many papers on neurological findings that I am not surprised Dr Wong did not mention it - especially given a lot of the biochemical effects of dystrophin deficiency/neurological involvement are still largely unchartered territory. (A lot of the work can only be done on biopsies of neural tissue, so it obviously is a lot harder to evaluate the role of dystrophin in the brain, as human neural tissue is not something that is readily available)

On the information given your son would have an out of frame deletion, requiring skipping of exon 51 to restore the reading frame.... given the location of his mutation, he should not be producing Dp140 if all current research is correct (based on the findings that the initiation codon is in exon 51, and you are out of frame from 47 onwards.....) therefore even though your son has the promoter site (where the RNAP binds to create the mRNA)transcription will be halted when it hits the nonsense region at 48/51. Therefore there is no initiation codon and no translation of Dp140.

Keep in mind that when it comes to neurological conditions associated with DMD, they are similar to the muscle progression in that there is a broad spectrum (as shown in the presention link I put up) and even boys with the same mutation will not necessarily exhibit the same neurological involvement. A lot of this is due to the altered pathways created during neurogenesis (no two pathways are the same when there is a deficient protein), and the subsequent effect this has on our boys. Also Dp140 is but one of the 7 isoforms of dystrophin sequestered in brain tissue, and there are a lot of factors affecting the expression of these proteins - even in boys with nonsense mutations.

Therefore the "source" of the neurological involvement is not easily defined, and could even come down to interactions with other proteins as well. Utrophin does has counter parts to the shorter isoforms, but again how this affects neural function is not yet fully understood.

The most important thing is to recognise the end result of dystrophin deficiency, and what this means to each child's neurological function, and develop strategies to compensate for any changes in the neural processes. We have been doing this with our son for 4 years, and whilst there have been challenges along the way, the benefits and improvements in his overall demeanour and school grade are immense.

Hope that helps :)

Wyatt's Mommy, Melissa said:
My question is then, does the child have to be missing all of 45 - 52 or a combination that fits into those numbers?. My son is missing 49 and 50. How does that effect him. I asked Dr. Wong about this subject because our 13 year old who doesn't have DMD is on the Austism Spectrum and she told me because we have a family history there is a SMALL possiblity, but she never mentioned this 2006 summary. (She may not no about it of course, but I got the sense it's not anything to really be concerned about. Obviously the DMD is such a bigger issue than Autism.)
Ofelia, You are right. Though boys with DMD have similiar situations, EACH child, EACH case is different, but I think the more information we have the better, so if our boys do begin to show some of these behaviors we can get intervention immediately, in order to minimize those symptoms.

Ofelia Marin said:
One thing I would like to mention is that NOT all the boys with deletions in that region (not producing Dp140) have learning disabilities and/or fall on the autism spectrum. I do know several boys with deletions involving hinge 3 w/o learning disabilities or autism. I assume that is the reason why doctors monitor each child individually w/o making assumptions about the location of the mutation and cognitive problems (except MAYBE for mutations close to the end of the gene where Dp71 is not produced).

Wyatt's Mommy, Melissa said:
Of course there are so many variables, I understand that, Dr. Wong telling me there was a possiblity was enough for me to pay attention. Thankfully I know what to look for so if we have to cross that bridge we will. Your information was very helpful thank you.

Julie Gilmore said:
Hi Melissa,

There are so many papers on neurological findings that I am not surprised Dr Wong did not mention it - especially given a lot of the biochemical effects of dystrophin deficiency/neurological involvement are still largely unchartered territory. (A lot of the work can only be done on biopsies of neural tissue, so it obviously is a lot harder to evaluate the role of dystrophin in the brain, as human neural tissue is not something that is readily available)

On the information given your son would have an out of frame deletion, requiring skipping of exon 51 to restore the reading frame.... given the location of his mutation, he should not be producing Dp140 if all current research is correct (based on the findings that the initiation codon is in exon 51, and you are out of frame from 47 onwards.....) therefore even though your son has the promoter site (where the RNAP binds to create the mRNA)transcription will be halted when it hits the nonsense region at 48/51. Therefore there is no initiation codon and no translation of Dp140.

Keep in mind that when it comes to neurological conditions associated with DMD, they are similar to the muscle progression in that there is a broad spectrum (as shown in the presention link I put up) and even boys with the same mutation will not necessarily exhibit the same neurological involvement. A lot of this is due to the altered pathways created during neurogenesis (no two pathways are the same when there is a deficient protein), and the subsequent effect this has on our boys. Also Dp140 is but one of the 7 isoforms of dystrophin sequestered in brain tissue, and there are a lot of factors affecting the expression of these proteins - even in boys with nonsense mutations.

Therefore the "source" of the neurological involvement is not easily defined, and could even come down to interactions with other proteins as well. Utrophin does has counter parts to the shorter isoforms, but again how this affects neural function is not yet fully understood.

The most important thing is to recognise the end result of dystrophin deficiency, and what this means to each child's neurological function, and develop strategies to compensate for any changes in the neural processes. We have been doing this with our son for 4 years, and whilst there have been challenges along the way, the benefits and improvements in his overall demeanour and school grade are immense.

Hope that helps :)

Wyatt's Mommy, Melissa said:
My question is then, does the child have to be missing all of 45 - 52 or a combination that fits into those numbers?. My son is missing 49 and 50. How does that effect him. I asked Dr. Wong about this subject because our 13 year old who doesn't have DMD is on the Austism Spectrum and she told me because we have a family history there is a SMALL possiblity, but she never mentioned this 2006 summary. (She may not no about it of course, but I got the sense it's not anything to really be concerned about. Obviously the DMD is such a bigger issue than Autism.)
I agree!

Wyatt's Mommy, Melissa said:
Ofelia, You are right. Though boys with DMD have similiar situations, EACH child, EACH case is different, but I think the more information we have the better, so if our boys do begin to show some of these behaviors we can get intervention immediately, in order to minimize those symptoms.

Ofelia Marin said:
One thing I would like to mention is that NOT all the boys with deletions in that region (not producing Dp140) have learning disabilities and/or fall on the autism spectrum. I do know several boys with deletions involving hinge 3 w/o learning disabilities or autism. I assume that is the reason why doctors monitor each child individually w/o making assumptions about the location of the mutation and cognitive problems (except MAYBE for mutations close to the end of the gene where Dp71 is not produced).

Wyatt's Mommy, Melissa said:
Of course there are so many variables, I understand that, Dr. Wong telling me there was a possiblity was enough for me to pay attention. Thankfully I know what to look for so if we have to cross that bridge we will. Your information was very helpful thank you.

Julie Gilmore said:
Hi Melissa,

There are so many papers on neurological findings that I am not surprised Dr Wong did not mention it - especially given a lot of the biochemical effects of dystrophin deficiency/neurological involvement are still largely unchartered territory. (A lot of the work can only be done on biopsies of neural tissue, so it obviously is a lot harder to evaluate the role of dystrophin in the brain, as human neural tissue is not something that is readily available)

On the information given your son would have an out of frame deletion, requiring skipping of exon 51 to restore the reading frame.... given the location of his mutation, he should not be producing Dp140 if all current research is correct (based on the findings that the initiation codon is in exon 51, and you are out of frame from 47 onwards.....) therefore even though your son has the promoter site (where the RNAP binds to create the mRNA)transcription will be halted when it hits the nonsense region at 48/51. Therefore there is no initiation codon and no translation of Dp140.

Keep in mind that when it comes to neurological conditions associated with DMD, they are similar to the muscle progression in that there is a broad spectrum (as shown in the presention link I put up) and even boys with the same mutation will not necessarily exhibit the same neurological involvement. A lot of this is due to the altered pathways created during neurogenesis (no two pathways are the same when there is a deficient protein), and the subsequent effect this has on our boys. Also Dp140 is but one of the 7 isoforms of dystrophin sequestered in brain tissue, and there are a lot of factors affecting the expression of these proteins - even in boys with nonsense mutations.

Therefore the "source" of the neurological involvement is not easily defined, and could even come down to interactions with other proteins as well. Utrophin does has counter parts to the shorter isoforms, but again how this affects neural function is not yet fully understood.

The most important thing is to recognise the end result of dystrophin deficiency, and what this means to each child's neurological function, and develop strategies to compensate for any changes in the neural processes. We have been doing this with our son for 4 years, and whilst there have been challenges along the way, the benefits and improvements in his overall demeanour and school grade are immense.

Hope that helps :)

Wyatt's Mommy, Melissa said:
My question is then, does the child have to be missing all of 45 - 52 or a combination that fits into those numbers?. My son is missing 49 and 50. How does that effect him. I asked Dr. Wong about this subject because our 13 year old who doesn't have DMD is on the Austism Spectrum and she told me because we have a family history there is a SMALL possiblity, but she never mentioned this 2006 summary. (She may not no about it of course, but I got the sense it's not anything to really be concerned about. Obviously the DMD is such a bigger issue than Autism.)
Your son sounds sooo much like mine! How do you do it, i mean how do you handle all that emotion and stress? What have you done for him for schooling?

Karen Barnett said:
My son is slower. Has speech delays, social immaturity and learning disabilites. He also has OCD and extreme tactile sensitivies. Very riged in his thinking and has trouble controlling his emotions. He is not autistic but some of his behaviors are said to be like autism. I believe his brain is affected by the lack of dystrophin to the brain. His personality/charecteristics follow many that are outlined with the psychological profile of what is written about many DMD boys and what I have read from other parents.

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