What will happen?

randford · Jul 11, 2006

Hello Everyone, 
 
I wondering what kind of health issues are there for all of us who
are heterozygous for Delta F-508 and a mutation of that gene
that creates CF? 
 
I was recently diagnosed and sInce my combination is so rare, Delta
F-508 and P-140S, I'm wondering what I should expect. I did find
this article and it does shed some light.
http://www.findarticles.com/p/articles/mi_qa4085/is_200505/ai_n13636341 

 
Also, How do I find out what class my genes rank?
thelizardqueen was kind enough to share the rankings: 
 
Genes are divided into Class categories 1-5. 1 being most severe, 5
being less severe when it comes to digestive problems. Here is a
breakdown: 
 
Class 1 mutations - Defective protein production with premature
termination of CFTR production. Class 1 mutations produce few or no
functioning CFTR chloride channels. 
 
Class 2 mutations - Defective trafficking of CFTR so that it does
not reach the apical surface membrane where it is intended to
function. 
 
Class 3 mutations - Defective regulation of CFTR even though it is
able to reach the apical cell surface. 
 
Class 4 mutations - CFTR reaches the apical surface but conduction
through the channel is defective. 
 
Class 5 mutations - Associated with reduced synthesis of functional
CFTR. 
 
Thanks! 
 
Randford, 43/male/CF

wanderlost · Jul 11, 2006

I have delta F508 and ....I always forget - S549 or something like that. I belive they are both class II mutations. I have been pretty healthy so far - no IVs or hospitalizations as of yet, minimal time spent on antibiotics, no inahled meds - except hypertonic saline - don't know how much is the genetics of Cf and how much of that is just good genes (knock on wood).

NoExcuses · Jul 12, 2006

Don't be fooled - your CF gene combinations are no where near a good predictor on what to expect with your CF.

There are many people on this site, and with CF all over the world, that have the same gene combination but different clinical outcomes.

Issues like modifier genes, food intake, environment, compliance with meds, can affect your clinical outcome.

Landy · Jul 12, 2006

I have to agree with Amy here.
There are many, many cases where siblings have the same identical genes and completely different severities of CF....such as my late sister & myself.
I really don't put a whole lot of stock in the fact that I have one of the more 'severe' mutations. I figure what will be will be.
Just my opinion.

Alyssa · Jul 12, 2006

Randford,

Excellent question ! Haven't we all wondered the same thing !!!

What Amy said is true, however I believe it is normal human nature to want to try and figure out what the future holds for all of us or what we think our "odds" of this or that happening to us are going to be, so I understand where you are coming from. As a parent of two late diagnosed children (age 13 & 18 yrs old) I know I was hungry for the same type of information at the time of diagnosis. My daughter's first question after hearing the news was "is CF a progressive disease", nothing like starting off with the toughest one to say yes to huh?

You could read my blog - I talk in more detail there about my kids and their health issues (or lack there of) -- all the info is in my signature line

They are DeltaF508 7T & R117H. I cannot remember for sure, but I think the DeltaF508 is a class 5 and the R117H is a class 2, but I could be completely wrong about that. I do know that there doctor has said that the R117H is the more "mild variant" gene and is what is helping to keep them healthier than some other people w/ CF.

**updated**
Well, according to LouLou's post on another question about gene class, I was wrong about my kids mutation class -- her post has them ranked as
Delta F508 class 2
R117h class 4

thelizardqueen · Jul 12, 2006

Well I'm double delta f508, and I've only been hospitalized 2x for lung issues. I've also only been hospitalized a couple of times for digestive issues as well, and that was when I was 6 and 8 for digestive issues, and 15 and 24 for lung issues.

randford · Jul 12, 2006

Amy, 
 
Amy, you are absolutely right when you said "Issues like
modifier genes, food intake, environment, compliance with meds, can
affect your clinical outcome." I agree. Even androgen levels
can affect CFTR expression as I discovered from the CF
endocrinologist. 
 
I'm still learning. Among other things, the CF regulating gene,
Transforming Growth Factor Beta -1. It regulates the severity of CF
according to a study by the University of North Carolina at Chapel
Hill. Here is the link. Go to the 10/3/05 release: <a
onclick=
"window.open('http://www.cff.org/Action/act_GetContent.cfm?ID=5932&FILE=UNC%20NEJ%2010%2D03%2D05%2Epdf&TYPE=2562','newWindow','statusbar,scrollbars,menubar,titlebar=no,resizable')"
class="contentarealink" href="javascript:void(0)">UNC Study Proves
Genetic Variations Influence Severity of CF</a> 
 
This is the page link: 
http://www.cff.org/news/press%5Froom/2005%5Fpress%5Froom/ 
 
Here is another link: 
http://www.eurekalert.org/pub_releases/2005-10/uonc-spg100305.php 

 
"The study, led by University of North Carolina at Chapel Hill
and Case Western Reserve University researchers, for the first time
shows that particular versions of the transforming growth factor
beta 1 (TGFb1) gene are largely responsible for how badly the
illness affects patients' lungs." 
 
As Lynda and Alyssa have indicated, there
is really no way of knowing what progression of the disease that I
will have as compared to anyone else. The fact that my combination
is so rare makes it even more difficult. It's like driving at night
without headlights. 
 
What I do understand is that with each event, be it pulmonary or
otherwise, you never fully recover to your former state. So being
proactive with medication and environment is most important. Now I
have to be very careful and aware. It drives me crazy but I have no
choice. 
 
I'm getting off topic but I can tell you that I can no longer visit
with friends at the local pub where there is smoking. Several of my
friends smoke and it was most uncomfortable and probably unfair to
ask them not to smoke for that amount of time. That is their
recreation. I don't agree with smoking nor does it agree with
me. I never understood why I despised smokers my whole life. I
always had such a bad reaction second-hand smoke...now I know
why. 
 
God, I don't know what to think about all of this. I get concerned,
I get angry, sad, then resolve. The cycle of emotions never
stops. I just don't know what to expect. I've only been
diagnosed since April but I've had problems for years. That's what
led up to this. Plus, had it not been for my Nephew, God rest his
soul, I never would have known. He died from CF last year. 
 
Thanks for all of your support. I digress. Give me time. I'm still
learning. 
 
Randford 43/CF

Alyssa · Jul 13, 2006

Quote by Randford:
"What I do understand is that with each event, be it pulmonary or
otherwise, you never fully recover to your former state. "

** Well, that statement is true some of the time, but I don't think it is always true - I think it depends on your age, health and how bad the "episode" is among other factors already talked about.

My daughter of course isn't always the best one to use as an example, but her lung function has improved over the 4 years since she was diagnosed, thanks to pulmozyme, flovent & the vest. She has had fewer lung infections since diagnosis too, so I would have to say that she has, so far, always recovered to her former state after a lung or sinus infection. Granted, she only was treated with oral antibiotics and one round of inhaled Tobi for one bout with non-mucoid pseudomonas.

amber682 · Jul 13, 2006

My son has DeltaF508, inherited from me, but the gene inherited
from his father is not known. The cf clinic even sent a sample out
for genotyping to California (we live in RI) and it when I asked
the doc what came back he said they couldn't id it. When I
was pregnant I tested as a carrier but my husband did not, so we
thought we were in the clear. My son wasn't diagnosed until he got
RSV at 3 mos. that would not get better. (I've got a great story
about that for another time, about going with your gut!) So
any family members related to my husband who wanted to know if they
were carriers, like he is, would just come back neg too, right?
Even with a test that tested for more
mutations? But it drives me nuts cuz I don't
know how severe his cf is, according to the gene classifications.
Plus, since Delta f508 is the most common, if there's a cure
for that mutation in say 10 yrs. how much longer would it take with
all the least common or unknown mutations? These are the kind of
things that keep me up at
night<img src="">

randford · Jul 15, 2006

Alyssa, 
 
That's comforting. I just cannot afford treatment at the moment. I
just hope I hold it together until I can. I should be on Pulmozyme
now. 
 
As for you daughter. I am so glad she is doing better. Keeping
children on a regiment is difficult, especially when they are in
their teens. My Nephew was stubborn but we kept him on focus. Just
keep both of them on point. Eventually, new treatments will be
available. Pseudomonas is our enemy. It's like pushing a car
uphill. If you lose traction, it can roll back on you. But I'm
preaching to the choir. 
 
Thanks for the info. 
 
Randford, 43/CF

randford · Jul 15, 2006

amber682 
 
Wow, that is amazing and stressful I'm sure. Boy, I learn something
every day. That's quite a situation when the mutation is so rare,
it cannot be identified. Then different combinations bring
about different symptoms. Then we are all biochemically different.
Add those 30,000 gene modifiers and the TGF beta-1 gene and there
is really no telling what to expect. I swear, for me it's like a
time bomb. I'm OK now but who knows. I'm right there with you. It
drives me nuts as well. 
 
Randford, 43/CF

Landy · Jul 15, 2006

Randford,
You had mentioned needing Pulmozyme.
I took it a couple of years ago and at that time there was an endowment program that helped me pay for my Pulmozyme based on my income (no matter if you're on the low or mid/high income level).
Since I don't do Pulmozyme anymore, I'm not sure if that progrom still exists but I will give you the information & it would be worth a phone call to see if they could help you with the cost.
The Genentech Endowment for Cystic Fibrosis
P.O. Box 222157
Charlotte, NC 28222
1-800-297-5557 phone
1-704-357-0036 fax
Possibly it would be beneficial to others if you would share if the program still exists or not as others may need help paying for Pulmozyme & are unaware of the program.
Also, I'm assuming you're in contact with the social worker at your CF Clinic so they can keep you informed of any state-aid type programs to assist with meds/etc?

LauraM · Jul 16, 2006

Amber - don't worry about the fact that it may take a long time for your son's rare mutation to be cured. Only one gene needs to function to cure CF (at least that's what they're hoping!) so as your son has deltaF508 this gene can be corrected and then he will only be a CF carrier rather than a sufferer.

amber682 · Jul 17, 2006

I'm not sure if Vinny had the Ambry test though, I was just reading
about it online. I'm going to find out next visit to the clinic.
 
 
Laura, I hadn't thought of that. Thanks, it put me a little more at
ease.

What will happen?

randford

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wanderlost

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NoExcuses

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Landy

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Alyssa

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thelizardqueen

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randford

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Alyssa

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amber682

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randford

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randford

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Landy

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LauraM

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amber682

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