Hi, I was just wondering if anyone can help interpret my son's genetic report. I requested this from his doctor. She did originally give us a pretty good idea of what we were looking at by using the alphabet, but I am just wondering if there's anything we need to press further at his next appointment which is September 23rd. He has pretty subtle symptoms and his cpk level at diagnosis was 4487. We are now on deflazacort and are going to be going through testing in December I believe for the PTC 124 trial.

from University of Iowa:
Kyle has a point mutation that resulted in a premature stop codon which is also known as a nonsense mutation. This mutation is present in exon 58 of the dystrophin gene. The report tells us the specific site/position in the gene that the change occurred (at position 8608 a single nucleotide change occurred. Cytosine changed to thymine).

The DNA “letters” (C, T, G, A) are grouped in sets of 3 and are called codons. The codons code for amino acids and strings of amino acids make up proteins. There are three codons that code for amino acids that terminate translation of the code into amino acids & proteins……this stop in translation needs to come at the end of the gene. A stop mutation within the gene means the sequence is cut short.

Here is Kyle’s genetic testing report:

INTERPRETATION:

It is our understanding that based on clinical and/or laboratory findings, this patient has been given a probable or definite diagnosis of Duchenne or Becker muscular dystrophy. For the purpose of interpreting our data, we assume that this diagnosis is accurate.

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DNA extracted from a blood sample from this individual has been examined by 1) high density DMD Oligonucleotide Array Comparative Genomic Hybridization (array-CGH) and 2) Multiplex Ligation-dependent Probe Amplification (MLPA) of all 79 dystrophin exons. Discordant results were obtained by these methodologies. While MLPA failed to detect exon 58 of the DMD gene, array-CGH showed a normal hybridization pattern in this patient. Sequence analysis of exon 58 was therefore performed to clarify

these discrepant results.

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This sequence analysis identified a hemizygous C to T change at nucleotide 8608 (c.8608C>T) in exon 58 of the DMD gene. This nucleotide change lies in the MLPA exon 58 probe ligation site and appears to account for the observed failure of amplification of exon 58 by MLPA. The c.8608C>T substitution results in an amino acid change of Arginine to a premature stop at codon 2870 (p.R2870X). This nonsense mutation has been previously reported in the Leiden Muscular Dystrophy Database (http://www.dmd.nl), and it is predicted to produce a premature translation termination. This nucleotide change is therefore interpreted as a disease-causing DMD mutation (ACMG Sequence Interpretation Guidelines, www.acmg.net).

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The identification of the c.8608C>T (p.R2870X) mutation confirms the clinical diagnosis of DMD/BMD in this individual. Carrier (test code 6085) and prenatal (test code 6139) risk assessments for this mutation could be offered to any at-risk adult or symptomatic female relatives using this DNA sequencing methodology. We recommend that the at-risk female relative be made aware of the availability of these studies. Genetic counseling is recommended.

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METHODOLOGY:

Dystrophin gene deletions account for approximately 60% and duplications for approximately 5% of affected males and carrier females for Duchenne/Becker Muscular Dystrophy. This individual has been evaluated for deletion and duplication mutations of the dystrophin gene by Southern Analysis of Hind III digested genomic DNA and/or high density DMD Oligonucleotide Array Comparative Genomic Hybridization. Densitometric investigations of Southern data may have been conducted. The reliability

of mutation analysis on females is not as good as similar analysis on males. DNA studies do not constitute a definitive test or precise carrier test for DMD/BMD in all families. Thus, the interpretation of molecular data may be reported as a probability. Linkage analysis takes into account the chance for an unidentified recombination which is 5% if only 5' and central or 3' and central alleles are informative, 1% if all regions are informative, and 10% if only 5' or 3' alleles are informative.

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Hi Donna,

Wow! That is quite a lot to digest. Have you tried speaking to a genetic specialist at DuchenneConnect? They make this stuff easier to digest and are completely free of charge to those who are registered, possibly others. We registered and have contacted them more than a few times in the past months. They are easily reached by phone or e-mail. Calling them worked best for me because I need a persons voice in order to read tone and emphasis.

best of luck!
cheryl
how do I get a hold of them and/or register with them?
cheryl cliff said:
Hi Donna,

Wow! That is quite a lot to digest. Have you tried speaking to a genetic specialist at DuchenneConnect? They make this stuff easier to digest and are completely free of charge to those who are registered, possibly others. We registered and have contacted them more than a few times in the past months. They are easily reached by phone or e-mail. Calling them worked best for me because I need a persons voice in order to read tone and emphasis.

best of luck!
cheryl
Oh, sorry I didn't include that previously. Check for them at the PPMD main page, I they are a simple click away. Registering is simple - and something that helps ALL DMD boys! Let me know if you need more help getting started, it really is easy.
cheryl

Donna said:
how do I get a hold of them and/or register with them?
cheryl cliff said:
Hi Donna,

Wow! That is quite a lot to digest. Have you tried speaking to a genetic specialist at DuchenneConnect? They make this stuff easier to digest and are completely free of charge to those who are registered, possibly others. We registered and have contacted them more than a few times in the past months. They are easily reached by phone or e-mail. Calling them worked best for me because I need a persons voice in order to read tone and emphasis.

best of luck!
cheryl
Here is the DuchenneConnect website: https://www.duchenneconnect.org/

There are only 2 things that you really need to understand about your report.

1. Your son has a Nonsense mutation. In our DMD world, this is a good thing. The drug they want to get your son in trial for (PTC-124) is the 1st drug that may cure around 13% of duchenne patients. That 13% are only those who have a nonsense mutation and they are pretty far along in trials. If all goes as planned, 2011 or 2012 will be a good year for those 13%.

2. You need to be tested to see if you are a carrier or not. With the identification of the location of your sons mutation (did that sound like Don King?), the lab will be able to look in the exact same location on your X chromosomes to see if you are a carrier. If it comes back that you are a carrier, then it is a good idea if you have sisters that they get tested and if you have daughters, that they get tested. At least everyone would know whether or not they are carriers and can make decisions on how they want to go about having children.

Other than that, all the numbers, symbols, and medical jargon is just that, jargon that we really don't need to understand.

Hope this helps,

Christian

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