My son Francis has DMD and has a splicing mutation. I wanted to know if anyone could explain it to me better? Is there another parent of a son with DMD that has a splicing mutation? I would love to hear from you.
God Bless,
Suzanne

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From Wikipedia: http://en.wikipedia.org/wiki/Splice_site_mutation
"A splice site mutation is a genetic mutation that inserts or deletes a number of nucleotides in the specific site at which splicing of an intron takes place during the processing of precursor messenger RNA into mature messenger RNA. The abolishment of the splicing site results in one or more introns remaining in mature mRNA and may lead to the production of aberrant proteins. Several genetic diseases may be the result of splice site mutations."

Deletion is the more popluar of the 2 underlined in the quote above. If your son has a deletion, then he would be missing 1 or more exons in the Dystrophin gene, which has 79 exons. Using a small sentence made of 3 letter words as an example (each word is an exon), a deletion would be like this:

Original: The fat cat ate the wee rat.
Deletion: The fat ate the wee rat. (cat is deleted)

As for an Insertion: Insertion is the addition of one or more nucleotide base pairs into a genetic sequence. So, here's an example by inserting one word (exon) into the sequence:

Original: The fat cat ate the wee rat.
Insertion: The fat cat xlw ate the wee rat.

These examples were found from this site: http://www.genetichealth.com/G101_Changes_in_DNA.shtml

Hope this helps.

-Christian
Hi Christian,

What steps did you take to find out if your son has Deletion or Insertion? You have started to help me see the light. I did not know that there were two types regarding this subject. Are you going to the PPMD Convention in Philadelphia?
God Bless,
Suzanne
Hi Suzanne,

My sons Neurologist that diagnosed him told us. Yours should know as well and be able to tell you. Give him/her a call and find out the exact mutation. They should have told you this along with which exon(s) are part of the mutation.

I am gonna guess it's a deletion. I don't think I have ever read from a parent who said their son has an insertion.

Two other types of mutations we normally hear about with DMD are Duplications (exon(s) are duplicated) and Nonsense...A.K.A. a premature Stop Codon (that would be like putting the period of a sentence somwehere in the middle, causing the sentence to suddenly just stop).

As for conference, yes, we'll be there.

Take care,

Christian
Here is a list of Splice Mutations from the University of Utah Genome Center. http://www.genome.utah.edu/DMD/mutation_tables.cgi?table=SPLICE.csv

The definition they have on their site is: Splice: any change that effects the splicing mechanism.

So, definitely contact the doctor that diagnosed your son and ask for the exact mutation and location. You need to know in case of anything that comes down the pipeline that may benefit your son.
Hi, Suzanne.
My son has also got a splice site mutation. And here is what I have found out from a specialist:

``The genetic information to make the dystrophin protein is in 79 separate
blocks. These blocks need to be joined to make a functional gene message,
and the boundaries of these blocks (exons) are defined by splice sites. If
one of these splice sites has a mutation, it is not recognized by the cell
machinery responsible for joining the blocks together, and the block gets
excluded. Depending on which block is affected, it may be possible to by
pass the problem using one of the antisense oligos (currently in trial is AVI-4658).

What usually
happens is that the cell splicing machinery looks for the next bit of
sequence that looks a bit like a splice site, and it uses that. These
splice site mutations often cause a few different splicing patterns, because
the cell can't find a 'perfect' splice site. Exons get left out and this
may have the same result as a frame shift deletion, or bits of intron are
retained with the exon.''

Do you know what his mutation is exactly? Phillip's is c.6615-1G>C in nomenclature that is recommended by Leiden Muscular Dystrophy website.

Sofia
Hi Sofia,

Thank you very much for your information. I am having alot of difficulty finding someone to speak with to help me understand his mutation and narrow down which mutation it is in the first place. I'm sure your information will come in very usful when someone finally talks with me. I'm working on it. Thank you and everyone else who has helped me in this disscution.

Suzanne
Sofia Suvorova said:
Hi, Suzanne.
My son has also got a splice site mutation. And here is what I have found out from a specialist:

``The genetic information to make the dystrophin protein is in 79 separate
blocks. These blocks need to be joined to make a functional gene message,
and the boundaries of these blocks (exons) are defined by splice sites. If
one of these splice sites has a mutation, it is not recognized by the cell
machinery responsible for joining the blocks together, and the block gets
excluded. Depending on which block is affected, it may be possible to by
pass the problem using one of the antisense oligos (currently in trial is AVI-4658).

What usually
happens is that the cell splicing machinery looks for the next bit of
sequence that looks a bit like a splice site, and it uses that. These
splice site mutations often cause a few different splicing patterns, because
the cell can't find a 'perfect' splice site. Exons get left out and this
may have the same result as a frame shift deletion, or bits of intron are
retained with the exon.''

Do you know what his mutation is exactly? Phillip's is c.6615-1G>C in nomenclature that is recommended by Leiden Muscular Dystrophy website.

Sofia

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