Understanding the Genetics

[JustaCFmom]

Hi!
I am trying to understand why my daughter had such a high sweat test result of 71 and why carriers (or how carriers) are effected. She has 3 siblings with CF - W1282X, and 3649+10kb C>T which is the only reason she was tested. She is perfectly healthy. This result was a shock, the other nonCF siblings had normal levels (She is one of ten ). She carries the W1282X mutation.
Any explanation is greatly appreciated.

 

[JustaCFmom]

Understanding the Genetics- CORRECTION

OOPS, I got mixed up.
Her mutation is the 3849 +10 kb C>T , for what it's worth.

 

[Printer]

I can't explain but I can question. Did daughter have a FULL CF SEQUENCING. If she was tested differently than her siblings were, it would be possible that the scan did not include the second mutation.

When I was first tested, in the mid 1990s, (for only 250 mutations) they only found the Delta F508 mutation. When I was retested in 2011 (for almost 2000 mutations) they found the second mutation.

You may ask as to the number of mutations that they checked for.

Bill

 

[JustaCFmom]

I think they were all tested the same. 3 children have two mutations; 4 are carriers; and 3 have normal genes.

The doctor said that 70 is the high end of normal? What is CRMS? What does it mean? I hear people say a carrier isn't effected, but then there is this CRMS claim. Huh? Very confusing.
Any clarity?

 

[Mistyjo]

I was told 39 is the high end of normal. If you go to cuff.org I think it lists normal, borderline and positive results. My dd was 50 and we were told she is borderline or in the "grey".

 

[JENNYC]

I would tend to think that there was an error with her sweat test. I can't remember if I saw the post on here or facebook, but one mother that her child was taking Kalydeco went and got a sweat test after being on it for I think a month and was disappointed at the results because they were still high, so she had him tested again and it was amazingly low! So errors can be made with sweat tests. And since they know the 2 mutations that they would be looking for (that your other children have), I would think that they would know if she had them or not. But of course I guess a mistake could have been made there too. You heard about the woman who was diagnosed with the wrong mutation and it turned out she got retested and she had G551D instead of what they had told her. So I would think a mistake had been made somewhere because that does sound high for a sweat test. Just going off of everything that I've read on line. I have NO medical experience at all. <img src="i/expressions/face-icon-small-smile.gif" border="0">

 

[Mommafirst]

If all your kids have the same two bio parents, then I would think they would only test for the two mutations your known CF child has. 71 sweat is most definitely diagnostic -- it is NOT on the high end of normal at all!!! My daughter had 53, and has two mutations. Even though she is in the "borderline" sweat range, the docs said that there really isn't anything that would elevate sweats this much in her case, besides CF. If your kiddo has no symptoms and only one CF gene, I think I would want a repeat sweat test just to be sure. If it is still high, I would want full gene sequencing done instead of just the two mutations she was tested for. . . it is possible there is another gene in the mix.

 

[Printer]

I believe (and CF researchers agree) that my dad had undetected CF. If that is the case, while I got one mutation from each of my parents, my dad had an additional mutation. It is possible that a sibling could have received one, the same, mutation from my mom and a second mutation, different from mine, from my dad.

I would be looking for a full CF sequencing.

 

[JustaCFmom]

Thanks so much for your thoughtful replies!

I actually had a sweat result of 74 (2 times) so, while I don't have classical CF symptoms, there is something going on. I do have some minor respiratory issues They tested me for about 10 mutations and I have the 3849 +10 kb C>T mutation, which is what my daughter has (if they didn't make a mistake). I was expecting her to have the W1282X and some "invisible" mutation. My kids with the W1282X version seem basically healthy (but then so do I, so I don't know if I do have another mutation, what it means really)

I did a PFT & I got a FEV1 around 110, but the 25-75 part dropped to around 85%. After reading about all these trials talking about 10 % improvement, I suspect a 25% dip is significant. I live in a smoke free home which certainly helps!

Thanks again for your input. My daughter told me she isn't interested in pursuing this right now, but I will encourage her to repeat the test down the road, when she will be more open to it.