Welcome Ambry Genetics

[lilismom]

Hi Steve,
We just got the results of extensive genetic testing for my daughter. They found this deletion:
deleted exon #2(one copy) c.54-5811_c164+2186del8108ins182
I've found very little information about this particular mutation except that it has been found in CF patients in Sardinia.
Do you have any additional information on it?
She also has 1 copy of F508. The report the Dr gave me says these 2 mutations have not been found previously on the same chromosome.
Thanks
Sarah

 

[StevenKeiles]

Sarah,

Deletion of exon 2 is fairly rare, much more common is a deletion of both exon 2 and 3. either way when there is a deletion of 1 mor more exons it is like a classic severe CFTR mutation. In combination with a deltaF508 I would expect a typical CF presentation. And yes I would say it is very unlikely they are on the same chromosome.

Best of luck,

Steve

 

[JazzysMom]

STEVE.....

I want to thank you and any co workers that have helped members of CysticFibrosis.Com.

Your presence here has been a huge benefit to newly diagnosed as well as seasoned families.

Not only do you offer great knowledge, but the compassion that comes with your information is priceless.

HAPPY NEW YEAR TO YOU AND YOUR FAMILY!

 

[StevenKeiles]

Melissa and everyone else here at CF.com,

Thanks for the kind words they are much appreciated. I truly enjoy being able to provide support for people at what can be a very difficult time.

I would also like to wish everyone a very healthy and happy 2009.

Steve

 

[hmw]

Steve,

I have spent a while reading through quite a few pages of this thread. I am amazed by the knowledge that so many of you have in talking about this stuff <img src="i/expressions/face-icon-small-shocked.gif" border="0"> and thankful for how helpful Steve has been!

My dd was dx'ed with cf in Nov. at age 7.5 due to symptoms (severe growth failure being the primary one although respiratory infections have clearly worsened by the yr, in hindsight) leading to 2 positive sweat tests (90 & 108). Her brothers were then tested; one was neg. (34), one was borderline (48.) All 3 will be getting gene analysis done at your lab to determine her mutations and the status of the boys. As you can imagine I am really nervous about this...

At any rate I am wondering a few things: the primary problems she's had to date have been digestive ones. Are there specific mutations that seem to cause this, and while I know there are no hard and fast rules with cf... do there seem to be any trends toward whether or not they are more severe forms?

Secondly, as I am a carrier, I know one of my parents is as well. On my mothers' side, there is no one else of childbearing age that needs to worry about being tested. On my dads' side, however- I have multiple cousins of childbearing age. If my dad is ruled out as a carrier, can I assume that side of the family can relax? (I mean, I know one out of 30 or so Caucasians are carriers- what lengths should the 'average' person considering planning a family go in being screened?)

So lastly: once we know which ones my dd has- would it help my family (especially my brother, who is planning on getting tested for carrier status asap) to look for whatever specific mutations she turns up positive for, especially if they are some of the more rare ones?

Steve, again, thank you so much for how helpful you've been throughout this entire thread. I apologize if my questions have already been covered; there is so much I just do not know yet, and I just couldn't read through all of this!!

 

[StevenKeiles]

Harriett,

Yes there are some mutations that can be more associated with GI problems and of course there are some that are more severe than others.

With regard to who should be screened and how, it is probably best to wait for the first test results to come back and then depending on the results we can make appropriate recommendations for family members.

Steve

 

[hmw]

Thanks Steve. Our insurance approval went through and all three kids will be having their blood drawn tomorrow. Hopefully the mutations won't be too hard to find and we know what we are dealing with soon.

 

[valigirl21]

Jada, I'm in the same boat as you; the pulm is taking a wait and see attitude about my son, except he dosn't have any mutations, and no del/dupe were done...Which reminds me...

Steve,

What is the meaning of the deletion/duplications; you told me my son's testing did not include them. Would it change his dx if he had any? Would we finally get a definitive dx?

 

[StevenKeiles]

Valerie and others who wish to know.

Deletions and duplications are just specific types of mutations (usually severe ones) that make up about 1-2% of all CF mutations. they cannot be diagnosed using sequencing techniques, you must use different technology in order to check for these types of mutations. So in order to be complete you would need to have deletion testing to make sure there are no mutations or to identify these mutations. If you already find the two mutations on the sequence test then extra testing for deletions would not be required.

Steve

 

[NYCLawGirl]

Hi Steve,

I was diagnosed by sweat test at 6 weeks, but they were unable to find my second mutation for quite a while until they ran the complete deletion test, which I believe was in my teens. It appears I have DF508 and CFTRdele1-24 (complete absence of CFTR gene, in my understanding). Sometime in between the diagnosis and the discovery of my deletion we did carrier tests for my entire family.

My question is, now that we know my deletion, what is the value of rerunning the tests on other family members (specifically those not found to be carriers originally) to ascertain if they in fact carry the deletion? Do you think this would be difficult to push through insurance-wise? I have to think that since the deletion mutation is (in my understanding) even more severe than the DF508 mutation, and harder to diagnose once a child presents symptoms, it would be beneficial for my family members to know if they carry this mutation.

Thanks,
Piper

 

[StevenKeiles]

Piper,

The deletion is not necessarily more severe than deltaF508 but it is a severe mutation. yes it would certainly be beneficial to have siblings etc. tested for this mutation and it probably would be the same as other tests for family members as far as insurance is concerned. Which means some get covered and some don't. FYI, the deletion testing ends up costing about $760 so it is not as expensive as doing the full gene sequence.

best of luck,

Steve

 

[thiot2000]

Hi Steve,

WOW! I have spent the past two hours reading this thread. What a wealth of information here.

I have a question related to recommended testing. I am considering an egg donor who has been positively identified as a CF carrier, but I do not know the specifics of her mutations, etc. She was diagnosed after a sibling was born with CF. (I know some may wonder why we are considering her, but everything else is wonderful and she looks enough like me to be my sister.)

According to our RE, we are having a "full" Ambry genetics test done for CF mutations. I am wondering exactly what we are getting (I was told that the self-pay cost would be $1500.00). Should we ask for the 508 First test or is that commonly done before the CF Amplified test is done when doing CF Screening?

If my husband's CF Amplified testing indicatates no mutations, would you recommend that we ask the donor to complete the amplified testing? Do you have any other recommendations?

Thanks in advance for your advice.
Kim

 

[StevenKeiles]

Kim,

The 508First test turns into the CF Amplified test after checking for the deltaF508 so you end up with the same test. No need to do anything different now.

Since the donor is already known to be a carrier, no further testing would be necessary on her. If someone is negative on the CF amplified test the chance they are a carrier would be reduced to approximately 1 in 2400 and if the other parnter is a carrier, the risks to have a child with CF gets reduced to approximately 1 in 9600. This is 3-4 times less than the risk of any couple to have a child with CF in the general population. So even knowing the someone in the couple is a carrier of a CF mutation, if the other partner had a completely negative comprehensive CF test the risks to have a baby with CF are lower than the general population.

best of luck,

Steve

 

[akahl]

Hi Steve,
I have to tell you that this site has been the most interesting and most educational site I have come across. I am a 30 yr. old female diagnosed last week with CF. After my diagnosis I realized that the mild symptoms I have had my entire life are probably related to the CF (although I am not positive). The two mutations that were identified are Delta F508-9T and R117-7T. Can you tell me anything about these two mutations as a combination? Is it true that the mutation that "presents" itself is the one that your body is most likely affected by or do both mutations affect as a combination? Thank you in advance for your help ~ what a blessing you have been to so many people!

 

[StevenKeiles]

Actually, the combination of the two mutations is what causes the problems. The R117H mutation tends to be a milder mutation which is why you have milder symptoms presenting later in life and also why you were not diagnosed until more recently.

At least now you can be followed and treated correctly so that should help you as you get older.

Best of luck,

Steve

 

[hmw]

Well, I spoke to someone from my dd's clinic today and she mentioned that she'd found out Emily's test kit had arrived (for the CF Amplified) and was being run right now... now the waiting begins. The boys' test samples will be showing up shortly (we ended up not being able to do theirs the same day.)

Thank you Steve for being so responsive to all of us here. I have really enjoyed keeping up with this thread and being so new to this I have learned a lot.

 

[akahl]

One more quick question...
Are these two mutations typically associated with affecting the CFTR in certain ways. What I mean...Is the combo of the two related more closely to pulmonary or GI issues or is it a combination of the two?

Thank you!

 

[StevenKeiles]

It can go either way, there is always variability with all mutations so you can never know exactly as each person can be a little different.

Steve

 

[StevenKeiles]

It can go either way, there is always variability with all mutations so you can never know exactly as each person can be a little different.

Steve

 

[reagansmom]

Hello Steve,

My daughters doctor told us that her mutations were R1066C and 394delTNT. I've searched for them in the mutation database and did not find the mutation 394delTNT. However, there was a 394delTT. I thought that maybe I misunderstood her when she was telling them to me but my husband is sure that that's what she had written down. Any information you have that might help to clarify would be appreciated.

Thanks!