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sfzobie
08-28-2015, 11:09 PM
We have a recently diagnosed newborn with this rare combination. We have been fortunate enough to speak with several physicians both at Stanford and UCSF, we find ourself facing the great unknown.

Our daughter is 6 weeks old, had a positive newborn screening which resulted in the genetic sequencing. Her sweat test came back at 40, clear chest X-ray. normal labs and completely asymptomatic to this point. She is growing normally and had we not had the call from the doctors office, we wouldn't think anything was wrong.

I work in a unrelated field of medicine so I was able to get good access to the information available and it doesn't appear that there is a case documented of this mutation combination.

We are still awaiting the sequencing on my wife to see if she carries the rare gene as all of her pregnancy testing came back normal (DF508 would have shown up). Until that comes back we are just in a state of limbo since we don't know what this will end of meaning for her health down the road.

Just thought we would post to see if there were any other parents in our situation

Cheers

Z

triples15
08-29-2015, 02:04 AM
We have a recently diagnosed newborn with this rare combination. We have been fortunate enough to speak with several physicians both at Stanford and UCSF, we find ourself facing the great unknown.

Our daughter is 6 weeks old, had a positive newborn screening which resulted in the genetic sequencing. Her sweat test came back at 40, clear chest X-ray. normal labs and completely asymptomatic to this point. She is growing normally and had we not had the call from the doctors office, we wouldn't think anything was wrong.

I work in a unrelated field of medicine so I was able to get good access to the information available and it doesn't appear that there is a case documented of this mutation combination.

We are still awaiting the sequencing on my wife to see if she carries the rare gene as all of her pregnancy testing came back normal (DF508 would have shown up). Until that comes back we are just in a state of limbo since we don't know what this will end of meaning for her health down the road.

Just thought we would post to see if there were any other parents in our situation

Cheers

Z

Hi Z!

I'm afraid I'm not really the person you were looking for to respond, but I just wanted to say hello and welcome. :)

I'm so sorry to hear of your daughter's diagnosis, but so happy to hear it sounds like she is in VERY good hands with both her CF care team and her parents! As you know by now, there is no crystal ball in the world of CF. Two people (even siblings) with the same 2 genetic mutations can have very different outcomes. For that reason it can be very hard to predict what path of progression the disease will take. One thing we know, your pro-activity in her care will go a long way in helping keep her healthy.

Do you know what class of mutation D797A falls into? I'm sure you've read and heard about all of the very exciting drugs coming out that are mutation specific. I am a tad similar to your daughter in that I received one copy of DF508 from my dad, and a rare-ish one from my mom. My rarer is S945L, which is a residual function mutation. I'm hoping to get into a trial very soon of a drug that shows a lot of promise treating residual function mutations. I think very exciting, ground breaking things will continue to happen in the coming few years! And that's coming from someone who has been waiting for 34 years for something to get excited about! :)

Well I've gotta run. I'm sure some parents will chime in with more of what you are looking for. In the meantime, take care of, and above all ENJOY that sweet baby girl of yours!!

Autumn 34 w/CF -wife, and mom to a 3 year old little girl :)

Aboveallislove
08-29-2015, 09:24 AM
Welcome Z! First, congratulations on your precious daughter. I am so sorry to hear of the mutations, though. I did want to share some thoughts, although Iím in the "parent who got the newsborn screen and diagnosis of a baby" category, but not in the rare mutation category.

So, first, I wasnít clear on whether the clinic diagnosed her with CF finding D797A mutation a "cf-causing" mutation, or if you are in the limbo of whether they diagnosis CF or CF-related metabolic disease (I think the later is what its called). Personally, I donít like the later approach, unless the clinic also acts proactively...hereís why: If she has two mutations and a sweat test of 40, her CFTR isnít functioning properly, no matter what you call it. We know that lots happens in the small airways that we donít see for years and I and many here are very proactive.

The CFF has a diagnostic process which looks to whether it is a CF gene or unknown and it looks like a repeat sweat test is the next step in a couple of months.
https://www.cff.org/PDF-Archive/CF-Diagnostic-Process/ (https://www.cff.org/PDF-Archive/CF-Diagnostic-Process/)

I guess if you are in diagnostic limbo, what I would suggest is to have a discussion on how to be proactive, which to me would mean at a minimum Xopenex/Albuterol 2x a day and CPT.
On the other hand, if they have diagonised CF and are being proactive, having the rare mutation has two "big" impacts. First, you donít have a comparitve base to say "oh, this is a mild mutation." Two thoughts there: First, even mild need to be treated proactively, but second, given her low sweat test results (assuming repeat continues on the borderline/low range), she likely will has a mild mutation which is just wonderful. That said, as Autumn noted, there is such a range given the same mutations...I went into the sweat test knowing our son had two of the most severe mutations (df508), but at 6 he has "mild" CF lung involvement, but extreme aquagentic wrinklinger (per his doctor and our observation) and horrible (albeit now controlled) GI issues. Iíve read that 50% of phenotype is determined by genotype and 50% by environment...so DS likely has some great modifying genes lung and sinus wise and we do our part with proactive treatment and perfect compliance. Your daughter likely starts the genotype factor with an "ace" of having a more mild mutation. And thus, while you might not have the reassurance that thereís history to show she will have a mild case, it sounds very likely, but still needing to be proactive.

The second reason the rare mutation matters is that unfortunately the medicines that are just now coming out which treat the underlying cause of CF and repair the function of CFTR are approved based on gene mutation. I pulled the studies and her mutation isnít listed for the drugs currently being tested:

https://tools.cff.org/Display/dsp_ClinicalResearchHTML.cfm?id=405&IDH=9236776&State=&advancedSearchOn=true&ageshow=&status=&FEV1=&PSEUDOMONAS=&BCepacia=&PLT=0&Therapy=&Char=&Keyword=661

This wonít be an issue now and hopefully by the time sheís two or six when sheíd be ready for FDA approval, they will have it broaderly approved for those heterzygous for df508 and thus having a rarer gene wonít matter. And if it isnít quite there yet, you can still push and get covered off label drugs if her mutation fits in one of the class of mutations the drugs benefit.

Finally, and not related to the rare CF mutations question, I wanted to say that this early stage is so difficult. Everyone copes differently. For me, research helped and Iíve become a regular stalker of Vertex. Given your medical background, you might also want to read up on cystemine and Crispr https://en.wikipedia.org/wiki/CRISPR (https://en.wikipedia.org/wiki/CRISPR) (But obviously the more scientific stuff). The 661 drugs by Vertex (link above of upcoming research) have in vitro gotten CF function very high (want to say above 60%) and with CRISPR, thereís hope that before you send your daughter off to college they have sliced out the "bad" genes and inserted the good ones."

Please let me know if anything doesnít make sense or if thereís anything else that would be helpful to known. Fyi: At your stage I didnít know what I didnít know and wish I had just posted general threads of "any suggestions on how to handle enzymes", etc. as lots of lived and learned here.
Hugs and prayers,
Love

Printer
09-02-2015, 11:48 AM
I'm not a parent but I have CF. I have Delta F508 and a "milder" mutation. I'm 75, married for 53 years (this month) and a college graduate. I have and still lead an active life. I was a Commonwealth of Massachusetts Lifeguard for 5 years on an Atlantic Ocean beach.

The "unknown" that you are facing is not knowing how happy and successful your DD will become.

Bill

tweel
09-22-2015, 01:54 PM
Hi, I am Sfzobie's wife, and just wanted to correct his post: our daughter has the DF508 mutation along with the D979A mutation (not D797A)... In the hopes that someone else searches for 979, his post will pop up!
Thanks:)
Twee

triples15
09-22-2015, 02:32 PM
Hi, I am Sfzobie's wife, and just wanted to correct his post: our daughter has the DF508 mutation along with the D979A mutation (not D797A)... In the hopes that someone else searches for 979, his post will pop up!
Thanks:)
Twee

Hi there and welcome Twee!

Thanks for the updated info. When your husband originally posted this I checked the "sick kids" database, which is a database that catalogs and describes CF mutations and found nothing. With the mutation you provided there is a hit with some info and some published articles regarding that mutation.

http://www.genet.sickkids.on.ca/SearchPage.html

Sorry, I'm having some trouble with the link, so when you get to that page you have to choose "legacy name" and then type in D979A and it will bring up the info!

Best of luck to you, hope everything is going well with your new little one!

Autumn

triples15
09-22-2015, 02:38 PM
Me again, I think I fixed the link so it should take you directly to the mutation you are looking for. Then if you click on the "cDNA" name, it will take you to a page with a little more info and the link to the publications. :)

sfzobie
10-22-2015, 09:58 AM
Thank you all for the responses, and yes I did incorrectly list the secondary mutation incorrectly and it should be D979A.

In regards to our daughters health, there still has been zero symptoms and while she is growing rapidly, thus throwing off her height/weight ratio, she has been fine. They scale their H/W ratios based on typically smaller infants with hopes that they gain adequate weight. Since she is so tall, her weight is right at 50% but her height is about 90%, so the ratio is misleading. We supplement her breastmilk with formula and salt, per our nutritonist and she is gaining around 30g/day, which trends as normal.

At this point we are not starting any form of treatment, and our medical team concurs. We are following up at 6 months with repeated sweat, chest X-ray and labs. At that point if there is any change we will review our options for treatment.

Thanks for all your words and I will do a better job of checking the forums more frequently.

Thanks
Z