Welcome Ambry Genetics

[jennc0315]

Hi Steve,
My youngest son (11 months) has CF. His mutations are DF508 and G542X. I know that both of these are very severe mutations. My other son (5 years) passed his sweat test and although he doesnt show symptoms I have thought about getting genetic testing done to be 100% sure. My doctor said that if he had CF the sweat test would of come back positive because of the genes we carry (same mom and dad for both boys). Is this accurate?

Our clinic doesnt like to do carrier testing this young because they say some kids get depressed knowing they are carriers. Is this normal? They havent even offered to test us to see what mutations each of us carry.

Thanks
Jenn

 

[Happy1]

Hi Steve!
My son had the sweat test performed today. I printed out a sweat test procedure and commonly asked questions form from the Cystic Fibrosis Foundation site. In it I read sweat test values do not change from positive to negative or negative to positive as a person grows older.
In this forum I have read things about people who have rec'd negatives then later positives. Do you know anything about this? I was just wondering how much faith I should put in the results of this test.
The lab tech said yeah we got a little sweat today before we left today. We have no results yet. My son is 22months.

Thanks, Tiffani

I am the one who has a nephew with cf DeltaF508 also I am considering getting all of us tested to see if we are carriers. Could you give me some info on how to go about that? (me, my husband, and seven year old daughter)

 

[Juliet]

I was sweat tested at 19, scored a 53. When I was tested at 42, I scored a 40. Nobody thought I had CF until my genetic test results from Ambry came in. ~Juliet

 

[smccanl]

Hi Steve,

I am hoping you can give your opinion on my genetic test results (from Quest - I'd never heard of Ambry until finding this site). My allergist told me I was positive for a mild form of cystic fibrosis, but then said the CF doctor would decide.

My result was "Heterozygous for the p. R75Q CF variant and the p. G551D mutation." The lab interpretation is equivocal about whether R75Q causes disease. The lab also could not determine whether the variant and mutation were in cis or trans configurations, but said that having CF symptoms was consistent with trans.

So is this CF or not? I was tested because of chronic cough and sinusitis; the cough is only mildly responsive to asthma medicines. I have no detectable allergies. I am 32, with sinus issues my whole life and increasing lung issues in the last decade or so.

Also, my sweat test was borderline (64) but was a test for conductivity and not quantitative Cl concentration - the CF center said that they don't consider this test valid. The alpha-globulin deletion/duplication test was negative (none found); the results state that point mutations cannot be ruled out.

If the CF center tells me they do not need to see me, I'd like to know whether you think I should pursue a second opinion or drop the issue and start looking for a different cause of my symptoms.

Thanks so much,
Sarah

 

[StevenKeiles]

Jenn,

Given those mutations I would tend to agree with the clinic. If the sweats were very normal and they have no symptoms at age 5 it is unlikely he is affected. If he ever develops symptoms that could be related you could test him them.

Steve

 

[StevenKeiles]

Tiffani,

Wait for your sons results, I would recommend having him sequenced if the results are over 20. If he is very normal and you just want to get you and your husband tested I would recommend the 508First test that we offer. You can contact Ambry for more information on how to go about it.

Steve

 

[StevenKeiles]

Sara,
R75Q is a common variant that we have seen many times. We do not consider this a disease causing mutation. It is possible that there is something else in addition to the G551D or that this is contributing to some of your symptoms but I would not consider your exact results to be a form of CF. You may want to have a sweat chloride test at the CF center done to see where that comes back.

Steve

 

[smccanl]

Steve,

Thanks so much for the response. I have been reading both Quest's and Ambry's websites and they seem to claim different numbers of known mutations - I believe Ambry says it can detect around 1500 and Quest says it detects "all but 13 of the currently known 1006 mutations." I don't know if the website is out of date, the test is less complete, or the definitions of what constitutes a mutation are complicating things.

I don't know if you can comment on this, but if so, I'm curious whether an Ambry test would be more definitive. This would be no small issue for me, as I am pretty sure my insurance is not about to pay for ANOTHER complete CF gene sequence. But I would very much like to know... I really want to close this issue one way or the other.

Hopefully the CF center at USC will get back to my doctor soon as to whether or not they recommend further testing.

Thanks again,
Sarah

 

[StevenKeiles]

Sarah,

I cannot comment on exactly what they mean because to be honest I am not sure what they are talking about. If I had to guess I would think it is probably an out of date website. Regarding not testing for 13 mutations I would guess this refers to deletion testing. If you did not have that done then it should be ordered. We can do this test and it is actually part of our CF Amplified test. Quest can also do deletion testing if it has not been done already.

While no lab has more experience in testing the complete CF gene, I would not expect the results obtained from Quest to be any different than what Ambry would find. I certainly don't think you need another CF sequence test.

Steve

 

[Happy1]

Hi Steve Thanks for your response. His results were a 22 and They got very little sweat. What does sequencing mean??
Thanks, Tiffani

 

[StevenKeiles]

Sequencing is when you analyze the entire coding region of the CFTR gene to pick up the over 1500 mutations. It is just another term used to indicate the most comprehensive testing available.

steve

 

[combo76]

<begin quote><i>Originally posted by: <b>StevenKeiles</b></i>

combo76,



Polymorphism is another term for a common variant that is carried by a significant percentage of the population. they are not considered to be disease causing.



Steve, Thank you for answering me. When you write they are not disease causing, what are they? Do they cause symptoms of CF? Or other health related issues / but no disease, meaning no CF?

Thanks - Jenn

 

[StevenKeiles]

Jenn,

There are many variants that occur naturally in the population. Not everybody has exactly the same DNA, these are just some of the variants that make us all different. some are very rare and some are more common. It is possible that some of these do have other issues, but since many of these are so common it is difficult to know if there are any other affects. I would imagine over time we may learn more about different poly's.

Steve

 

[Gnome]

I have a few questions. You may have answered this before but I am just confused.

1. So are a variant and the Poly T value are the same?

2. Is there a difference between a variants and mutations?

3. My daughter was tested in Canada and was given Delta 508/IV58-9V as mutations. You told me earlier that IV58-9V is a common variant. Why did they give me a variant instead of mutation.

Sophie has Cf no question on that. I just am confused with how she is categorized. Family members ask me about the mutations and I just would like to know what I am talking about.

Thank You in advance

Nomi

 

[jbrandonAW]

Lemme just say I started to read through this WHOLE thread, I got to pag 12 and realized it went on forever...SO I'm just gonna ask my questions.

Steve,

I have CF, my mutations are G551D & 2184delA (any info on them would be cool). My husband was tested for 97 mutations - test came back neg. My daughter had the newborn screening done and was neg.

I didn't know at the time that they only tested for 97 out of 1500 mutations. So now I am interested in getting my daughter tested again. My CF doc said we just needed to have a sweat test done. How often does someone get a neg sweat test and still have CF??

Im very interested in having the Ambry test done.
My main question is about insurance. We have tricare prime, and I was curious what they pay, is it fully covered etc??

Thank you so much for all you help.

 

[semperfiohana]

i have been wondering the same thing as jessica for the insurance part that is. my husband was tested two years ago with the ambry panel and he is not a carrier. now that my son has been born i would like to know if he is a carrier or not. and if insurance (which i would assume if they covered it for austin before we were even married they would cover it now for our son) will cover it, how do i go about getting the things in motion for it? thanks!

 

[StevenKeiles]

sorry for the delay I was out of the office for the last week and had limited access.

Candice,

Your son is definitely a carrier since you carry two mutations, your son would be a carrier of one of them. Therefore there is no need to test him. Since your husband was negative, he should just be a carrier.


Jessica,

You can certainly have a negative sweat test and still have a form of CF. I would contact our insurance dept. and we can check on any insurance to determine benefits. Also both of the mutations you mentioned would be associated with a more typical form of CF.

Steve

 

[StevenKeiles]

Nomi,

I love your screen name. The poly T is a variant but the 5T acts like a mutation. I am guessing that your daughter has the 5T, you need to check the results because what you have written is not correct, it probably reads IVS8 5/9. or something like this with the 5 and 9 being the poly T's. The deltaF508 is on one chromosome with a 9T and the 5T is on the other chromosome. It is also important how many TG repeats are paired with the 5T, because if you have 11 it tends to be a very mild mutation and if you have 12 or 13 it becomes a more significant mutation.
If you need more information regarding TG repeats, I have explained this several times in other posts, just search for TG repeat.

I hope that helps.

Steve

 

[Mommy2Alysa]

Steven (Ambry)

My daughters both have DeltaF508 (from my husband) and G402X (from me, I think I remembered that correctly). I know you can not estimate how bad they are going to be healthwise but is there a mutation that is worse then others? Do you know anything about these two by chance?

 

[letefk]

Hi, Steve. First of all, thank you for answering all our questions. Your answers about the role of TG repeat in the 5T variant made me curious about something.

My daughters are both heterozygous Delta 508, with a M470V poloymorphism and the 5T/9T variant. Both are symptomatic, and both have cultured psuedomonas, so they were classified by the clinic as CF. After reading your comments on the role of TG repeat, I was curious about what role that might be playing in how the faulty gene is being expressed, and if the repeat was the same for both girls.

However, when I looked at the Ambry report, I could not find any mention of this. The results list only "Poly T variant: 5T/9T." I am just curious if this is a new piece of information, and something that would not have been noted on a test from 2005, or if I am simply not looking in the right place for the information. Thanks.