Welcome Ambry Genetics

[StevenKeiles]

Cdavis,

This is not a common mutation, but from the cases we have it appears to be a typical CF disease causing mutation.

Steve

 

[carrierae21]

My husband and I have been looking all over the internet trying to find a list of CFTR gene mutation classes.
alas, we gave up because we couldn't find one with our daughter's mutation on it. She has a DF508 which we know is a class 2, but her other mutation is 1898+1G>A and we can't find it on any lists anywhere. I know there are over 1,000 mutations so there may not be a conclusive list on the internet that we can find. I was just wondering if anyone else has this gene and knows for sure which class it is. Just curious. Thanks!

 

[StevenKeiles]

Carrie,

The 1898+1G>A is considered a class V mutation. I am not sure what that really means for you but I hope it helps.

I think the fact that this is a known typical CF causing mutation that can be associated with moderate to severe CF is probably more relevant.

Good luck,

Steve

 

[ColbysMom]

Does every CF patient have 2 mutations?? My son is 8 months old and has DeltaF508, but I am not sure if he has a second mutation??

 

[JazzysMom]

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

Does every CF patient have 2 mutations?? My son is 8 months old and has DeltaF508, but I am not sure if he has a second mutation??</end quote>

There must be 2 gene mutations. They can be the same or different. Since you only mention the delta F508, is it possible that he has both of them & its listed as DOUBLE Dekta F508 or DDF508?

 

[StevenKeiles]

Melissa is correct. If he really does have CF then he either has two deltaF508 mutations or he has another mutation that was not picked up on the newborn screening test.

Steve

 

[bdd9623]

Steven (Ambry)

I was wondering if you know if Children's Hospital of Philadelphia use the ambry test. My son just had genetic blood testing last week there and they didn't want us going to a quest or somewhere else for that matter. I was told 2 - 8 weeks.

 

[StevenKeiles]

Steven (Ambry)

They do use us sometimes. My guess is that we did not receive this one, so it must have gone to another lab.

Good luck,

Steve

 

[Shelbyville]

Steve:

RE: carrierae21
I'm a bit confused here beings this combination is a severe and a mild (class II & V)combination. It has been conjectured in studies that this type of combination will cause mild CF and most likely later in life. Am I confused with the classes or are there variations within the classes that really make the classification diminimus? Would it be correct to say the classification is the tag put the defect depending where it resides in the CFTR structure regardless of severity? That being said the class V defects would have significatly different outcomes. Well as you can see I'm very confused and just when things were starting to make sense.

Daised & Confused Steve

 

[StevenKeiles]

The 1898+1 mutation would not be considered a mild mutation but more classic mutation. Class V mutations are splicing mutations, some of which are severe and some of which are mild.

This all goes back to the point that I have made many times. The class of mutation does not predict anything, the same can be said for the mutations as well. Since two people with the same mutations can have very different disease.

Regarding what you have read, that is true but for only the milder mutations that fall into that category.

Hope that clears it up for you.

Steve

 

[Shelbyville]

Steve:

Yup I was confused with the classes and out comes. That helps a lot.

Thank You & Best Regards, Steven

 

[Gramma58]

Dr. Keiles, my grandson is 8 weeks old, and is just completing being tested and diagnosed. He was tested at birth and found to have slightly elevated IRT levels. His sweat test (last week) had a score of 24. He is completely healthy and has gained from 7# 6 oz at birth, to about 12 pounds now. He has clear lungs, good normal bowel movements, no symptoms at all. He sleeps and nurses well, is happy, and no one would have ever expected problems, but Tennessee screens newborns for CF. His genetic testing also just came back, as well as that of his mother and father. He has 3 gene mutations: R117H from his father and S1235R and R785X from his mother (she is only a carrier). Can you give me any info about this combination of genes--is this mild, more severe, or perhaps may have few or no symptoms? The CF physician who has examined him seems to think that he may never exhibit any symptoms (or that is what we wanted to hear!) Could this be? Should his 2 1/2 year old brother be tested? What decisions are facing my other daughter and her husband as they plan for a family?

 

[StevenKeiles]

Kathy,

The combination of the S1235R and R785X would be a severe mutation. However, having an R117H would be a mild mutation. It is not possible to know exactly what will happen, but the expectation is that with an R117H it could be anywhere from very mild to moderate.

Worthwhile to follow, but I would be optimistic and I would not expect any severe or classic type presenation.

Good luck,

Steve

 

[TB]

Do you have any information on C.2184_2185insA? I am having trouble finding anything I can pull up in full text. Thanks

 

[StevenKeiles]

TB,

this is also known as 2184insA, try looking under that. But I can tell you this is a fairly typical CF mutation that we see often. Of course as with all CF mutations there is variability so you can never predict the exact phenotype.

best of luck,

Steve

 

[TB]

Steve:

Thanks for the info on 2184insA. Is my understanding correct that this is a severe mutation? The other mutation my nephew has is DF508, which I also understand is classified as severe. However, he does not have the typical clinical presentation for either of these, as he has no pancreatic insufficiency at this time. What, if anything, would these two mutations lead us to expect clinically?

 

[StevenKeiles]

TB,

There is always variability with all mutations, so you can never predict what will happen. Also with CF it is not unusual for problems to get worse over time, so if he has no symptoms now that is good, but not a predictor of what will come. With these two mutations, you could see the range of a more moderate phenotype in some individuals and more severe in others.

Hope that helps.

Steve

 

[dlo2977]

Hi Steve. We just got my 3 year old daughter's mutation analysis back. She came back with one W1282X and one G551D. I have done some reading on these but wanted your input. She was just diagnosed and only has mild GI symptoms at this point. Thanks!

 

[StevenKeiles]

dlo,

Those are both fairly typical CF mutations so they can result in moderate to severe CF. The good news is that there are a couple of drugs that are targeting both of these mutations so hopefully there will be some new treatments in the coming years. Both drugs are currently in clinical trials so it will still be a little while before they get FDA approval.

Good luck,

Steve

 

[stringbean]

Steve,
I posted a question several months ago concerning my daughter's testing. At the time I wasn't sure who did the genetic testing, but recently was told that was done by Ambry and they did a full panel. My daughter has one mutation, N 5 UTR-152G. She also had 2 borderline sweat tests and she is PI.

The report from Ambry said that my daughter does not have CF but she is a carrier. The doctors have all told me that this test could not rule out CF, yet Ambry did. I'm curious why.

My daughter was adopted we have zero information about her biological family so recently went to see a geneticist. She ruled out any of the other syndromes that could explain my daughter's PI. Unfortunately, she was only able to get the doctor's notes when she requested our medical records, so she couldn't explain to me why CF has been ruled out. (She, by the way, wants us to go to another CF center, but is waiting to see the full report before sending us on.)

<i><b>I truly am not asking you for a diagnosis</b></i>. I'm thrilled to think that she doesn't have CF. I'm just trying to understand. I am wondering what it is about her particular mutation that leads Ambry to believe there couldn't be a second mutation lurking somewhere. Or is her mutation known not to cause any problems at all so even if she has a second mutation, it's unlikely to produce CF?

I really, really, really want to believe that she'll never get sick -- but I don't want to be cavalier about her health if there's any possibility that her symptoms could worsen over time. So I'm just trying to understand Ambry's conclusion that finding one mutation rules out CF.

Thanks!!!!