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misyvette · Jul 10, 2011

Hi Steve- I read this about one of my sons mutations 2183AA>G: 2183AA®G is a frameshift mutation characterized by the substitution of adenine for guanine (A®G) at DNA position 2183 and the deletion of an adenine at position 2184 in exon 13 (R domain) (Bozon et al., 1994; CFGAC, 1994). Now my question is: Since these two mutations correlate with one another.. if someone is tested negative for 2184delA, would than then rule out the possibility of them having the 2183AA>G mutation? Am I reading it right? do these two mutations correlate? does having 2183AA>G cause you then to have 2184delA? 

Yvette

Beofett · Jul 13, 2011

Steve,<div><div>My 10 month old son has been diagnosed with CF. The tests indicated a single DF508 mutation, and both 6T and 9T variants of the PolyT sequence.<div><div>He is pancreatic sufficient, and had high-normal/low-borderline sweat test results.<div>The lab results indicated that the 6T variant was "likely to be clinically significant", but I have not been able to find much information on that variant. Most of the references I found were related to polyT variants in conjunction with R117H mutation, and almost all of them were for the 5T/7T/9T variants.<div>Do you have any information on DF508/6T PolyT variant combinations?<div><div>Thanks,<div>Dave

fundraiser · Jul 21, 2011

I know this is in the wrong thread, but please read and help us find the cure! Thank you..

<A HREF="http://uk.virginmoneygiving.com/team/cureCF">http://uk.virginmoneygiving.com/team/cureCF</A>

Just copy and paste into your address bar.

StevenKeiles · Jul 22, 2011

Dave,

6T is very unusual. It is possible that it is significant, but it is all possible that the TG repeat may have an impact on this as well. Not sure who did the testing but you may want to have them address the TG issue and also double check that it really is 6T.

Steve

StevenKeiles · Jul 22, 2011

Yvette,

These are two different mutations, and you could actually have one of each on each chromosome. 

If the test was a sequencing test it would detect all of the mutations, if it was a panel test they would need to have both mutation on the panel to be sure.

Good luck,

Steve

StevenKeiles · Jul 22, 2011

LTA,
Since you already know your mutations, you do not need any additional testing.

Best of luck,

Steve

StevenKeiles · Jul 22, 2011

Johanna,

yes it means he was tested for 42 mutations, and yes he does not have 2 deltaF508 mutations since that would have been seen. 

it is really important to determine the sweat level. I am guessing by now you have a sweat test result which has helped to clarify the status. If that is elevated or questionable they should order CF sequencing to check for all the other mutations.

Steve

StevenKeiles · Jul 22, 2011

Mommie2mickie

Yes the genetics are just one part of the puzzle. If the genetics are negative that does not mean that it is definitely not CF, however it is very unusual for us not to find at least 1 mutation on someone who has clinical symptoms of CF.

Steve

StevenKeiles · Jul 22, 2011

MistyJo,

The panel you refer to is not the 92 most common mutations, only the 92 mutations that happen to be on that panel. In fact, many of those mutations are very rare and in reality almost all of the CF mutations are rare. So it is really not that rare for someone to have 2 rare mutations.

If there is a suspicion, you should have full CF sequencing to make sure there are no other CF mutations identified.

best of luck,

Steve

StevenKeiles · Jul 22, 2011

You are correct, CF is a progressive disease, it never gets better over time, the best it can do it stay the same but given enough time it always gets worse.

Obviously, not following recommended treatments can certainly speed up the process. There is no way to predict in any one individual when something will happen or at what age will it progress more than others.
I hope this answers your questions.
I wish you the best of luck, 

Steve

StevenKeiles · Jul 22, 2011

LTA,

Articles are not written for lay people so I really can't help you there. Statistics don't mean anything. If I told you something was 1 in a million and you are the 1 then it is 100% for you.

All mutations are variable so you can never predict exactly in any one case. R334W is a more moderate mutation so I would expect most people not to have the most severe classic presentation with one of these mutations. But remember this is generally speaking.

Best of luck,

Steve

Beofett · Jul 25, 2011

<div>Steve,<div><div>Thank you very much for the response.<div>Could you please clarify what you mean by the TG repeat? Is this referring to having both 6T and 9T variants? <div><div>I believe the testing was done by Genzyme. Our specialist has taken the stance that an indication of "likely to be clinically significant" is sufficient reason to assume full CF, and to treat it as such (and we are fine with that; its better to be proactive in this case). However, when I questioned him on the genetics, he was spotty at best. If we need to get more details, or follow up with the lab, I would probably need to be able to communicate my concerns very clearly.<div><div>I can try to ask them to retest using Ambry, but I am not certain how the insurance will feel about covering it unless we can provide a really good justification.<div><div>Thanks again for your help!<div><div><begin quote>Originally posted by: StevenKeiles

Dave,

6T is very unusual. It is possible that it is significant, but it is all possible that the TG repeat may have an impact on this as well. Not sure who did the testing but you may want to have them address the TG issue and also double check that it really is 6T.

Steve
</end quote>

Babs · Aug 8, 2011

Does the type of mutation correlate to male infertility? My 23 yo son has two DF508 genes, per a 1992 genetic test. Any reason to have more genetic testing? Thank you.

ElenaFalcon · Aug 26, 2011

Steve, many thanks for your time and dedication.

My one year daughter was diagnosed with cf few months ago because of malnutrition, sweat test borderline and single Df508 (ex 11 CFTR). Direct sequencing test revealed another absolutely new mutation - p.Phe1078Ile - which has never been described in any database before. I was told that this is missense mutation in exon 20 cftr (c.3232t>a) and that this is not a stop-codon mutation, but it is not clear whether cftr function is abolished or residual. This mutation was not found in 110 unrelated CF chromosomes and that is how the dx was confirmed. The mutation has been entered into cftr database than.

Have you ever seen p.Phe1078Ile? Can you please point me in the direction of some resources for p.Phe1078Ile by itself, or in conjunction with single DF508?

Thank you,
Elena

StevenKeiles · Sep 1, 2011

Elena,

We have never seen that mutation, so there is really no information to give. It is obviously very rare and so I would not expect any significant literature to help explain it.

Sorry I couldn't be more helpful.


Babs,

All CFTR mutations can cause infertility so that is not a surprise. If you know there are two deltaF508 mutations there is no reason for more testing.

Good luck,

Steve

StevenKeiles · Sep 1, 2011

Beofett,

Not sure if testing needs to be repeated, maybe just clarified. I cannot comment on someone elses test results. You can have your doctor contact me directly if there are questions.

Steve

ByGrace · Sep 8, 2011

Steve,
Thank you so much for the time you put into answering our questions here. I have learned so much from reading through these posts.
I have one question of my own. My son recently had testing done at a military lab (pretty basic) and they found one DF508 and a 5T allele (9T being the other). There's no mention of a TG # and the results do say that "there's no way to tell if the DF508 and 5T are on different chromosomes without further testing." We do have a referral to see a geneticist, so we should have more definite answers soon. I read a couple of your comments in this forum from a few years ago that say DF508 is almost always with the 9T, of course, leaving the 5T on the opposite. Have you found any instances of the DF508 and 5T being on the same chromosome?
Thanks,
Pam

chicagocubsmom · Sep 8, 2011

Apologies if this question has been asked before but I couldn't find it during my search.

We have a son with CF, we know his two mutations. We are considering having other children through IVF and would want to screen embryos via PGD for those mutations.

I am not sure how to select a fertility clinic or what to ask for when we are researching fertility clinics. Are there some clinics that do a better job of PGD than others or use different genetic tests? We have heard stories about some parents going through PGD and STILL ending up with a baby with CF. How does this happen and in these cases, is the fertility clinic usually to blame via an error or did the genetic test fail?

chicagocubsmom · Sep 8, 2011

Apologies if this question has been asked before but I couldn't find it during my search.

We have a son with CF, we know his two mutations. We are considering having other children through IVF and would want to screen embryos via PGD for those mutations.

I am not sure how to select a fertility clinic or what to ask for when we are researching fertility clinics. Are there some clinics that do a better job of PGD than others or use different genetic tests? We have heard stories about some parents going through PGD and STILL ending up with a baby with CF. How does this happen and in these cases, is the fertility clinic usually to blame via an error or did the genetic test fail?

zinnia · Sep 26, 2011

Hi Steven, my son is 2 months old now, no symptoms or clinical picture yet, the Newborn Screening shows Immune Reactive Trypsinogen 129.0 ng / ml, We proceeded to genetic testing, which showed the following:

CF100+ mutation analysis.....Analysis not performed
Sequence analysis.................Heterozygous for F508 mutation in exon 10
MLPA analysis........................Negative
IVS8 Poly T tract analysis.....5T/7T
TG tract analysis....................12TG/11TG

Then at 8 weeks do sweat test : 49mmol.

He has no symptoms, the review does not say whether their genetic mutations are in cis or trans.

I've learned that usually F508 is associated with 9T, but shows 5T and 7T, no 9T.

How can we determine cis or trans?

Could be F508 and 5T12TG on the same chromosome?

If F508 and 5T are on the same chromosome, is a carrier, mean no sickness?

Do trypsinogen values are high in babies who are carriers?

Thanks in advance.

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