Welcome Ambry Genetics

[StevenKeiles]

To all the questions regarding specific information about a particular mutation.

If the mutation is not deltaF508, it is a rare mutation. some are more classic or severe, some are more moderate to mild. there is no way to predict exactly any one mutation or combination of mutations on how they will act in any one individual. Each case needs to be judged on its own. even siblings can be very different.
Most mutations are not categorized into a specific Class. Also all mutations in any given class are not the same with respect to severity. there is great variability in all mutations.
The best way to judge a mutation combination is to look into the mirror and if it is to try and predict what will happen in a newly diagnosed baby, unfortunately there is no way to predict what will happen in any one person, only time will tell.
I hope that helps everyone.

Steve

 

[StevenKeiles]

Hannah and others,

Mutations that end in an X are stop codon mutations and would be the target of a new drug from a company called PTC. the drug is ataluran and basically is treats stop codon mutations. You only need to have one of these X type mutations so it would apply to anyone who has one mutation that ends in an X. It is not FDA approved yet, but it is getting close. I am sure you will find out through the CFF if not the nightly news sooner.
best of luck to everyone.
Steve

 

[StevenKeiles]

Sorry the last one should have been to Hannah's mom.
Also, if a mutation has only been seen in a few families or less there is really no way to know more about the mutation and that is the case for many of the mutations you have all asked about.

see the above post, because even more common mutations cannot be predicted exaxctly.
Steve

 

[StevenKeiles]

kellysmith and any others.

I would say the test has really not changed at all in the last 5 years. However, if someone was tested prior to 2006 and there is still a suspicion of CF it would be a good idea to be retested, otherwise there is no reason to retest assuming the most comprehensive testing was ordered which is CF Amplified Test .

steve

 

[annalisa]

Hi Steve,
one of my daugher's mutation is R347P (class IV).
Could you please tell me if it doe sinvolves a "gating" defect?Could Kalydeco work for it??
thank you in advance,
annalisa

 

[StevenKeiles]

The drug may be useful for other mutations and they are being investigated right now. however, no other mutation has been approved for treatment other that G551D. The other mutations will have to be looked at on their own, not sure which ones will or won't qualify at this time.

Steve

 

[Taylersmom]

Hi Steve,
Thanks for all your help on here. I am trying to get clarification and I am getting conflicting answers. V520F? Class 3 mutation?
I know my sons other 17 171g>a is a classic cf, class 1, but they have changed the other mutations's class a couple times. Can you clarify for me?
Thanks again for all you do!

 

[edsmom]

Hi Steve,

My 3 year old was diagnosed at birth w/CF. He has one DF508 and one mutation that is insA2732. I was wondering if you knew anything about the latter..

Any info would be greatly appreciated!

Julia

 

[katie4byz]

Can I ask what are the chances of having a CF mutation if my sons sweat test results were 40 boarderline?

 

[katie4byz]

Can I ask what are the chances of having a CF mutation if my sons sweat test results were 40 boarderline?

 

[katie4byz]

Can I ask what are the chances of having a CF mutation if my sons sweat test results were 40 boarderline?

 

[daisy85]

I had posted this in the newly diagnosed section, but someone recommended that I post it here as well in the hopes of getting feedback from Steven. For the last 7 years, I have dealt with chronic sinus infections, headaches, stomach problems, and fatigue. I seem to catch everything that goes around, and one round of antibiotics almost never resolves infections. I have discovered that I have a primary immunodeficiency (primary means I was born with it, as opposed to an acquired immunodeficiency), but I have been doing immunoglobulin replacement therapy for that for a year and a half, and I'm still having the same symptoms, just not catching as many viruses. My hematologist thought to have me checked for CF, so I found a place through the Cystic Fibrosis Foundation and had the testing done. Long story short, my sweat test result was 30, which is not even technically borderline, but because of my symptoms the dr wanted to proceed with the genetic testing, and they found one mutation, 2184delA. They then checked me for large deletions and duplications, which all came back negative. The dr and genetic counselor told me that basically there's an emerging understanding that CF is a spectrum and that for some reason that they don't understand yet, some carriers have symptoms. They said that I'm on the extreme end of being symptomatic as a carrier, but that as of yet there is no way to treat carriers who have the symptoms of CF. The dr also told me that we can't be 100% sure that I don't have another mutation that is just very very rare or hasn't been discovered yet, in which case I'm on the mild end of having CF. So should I be waiting a few months and retesting in case some new mutations have been discovered? Should I be asking for futher testing (I can see through my insurance website that Ambry did the testing, but I can't tell whether the dr ordered full CF sequencing or not)? Or should I just accept that I'm in limbo and try to learn to live with my symptoms? I'm also wondering whether anyone out there is a symptomatic carrier as well and does receive treatment.

 

[imagine04]

Hi Steve. I posted shortly after we received the results of my sons genetic screen last January (2011) and have since actually gotten the report printed off and was wondering if there was any information related to his screening. Last time I had posted there wasn't any information on his second mutation that could be shared so i'm hoping that maybe there is something now. Mutations Identified: p.I1023_V1024del (p.ILE1023_Val1024) & deltaF508 Intron 8 polyT alleles: 9T/9T DNA change for p.p.I1023_V1024del:Exon 17a, c.3199del6 (c.3199_3204delATAGTG) I am just curious as to how his "rare" mutation has presented in other patients tho i am well aware that the differences can vary greatly from patient to patient. Also, being that his variants are 9T/9T and CBAVD is associated more closely to the 5T is this something that does still happen in those with the 9T's? Also, i'm curious as to what class his rare mutation would be considered?Thank you for any information you can share!

 

[MiahsMommy]

Hi Steve,
After my daughters diagnoses and learning about cf, I've noticed to have some similar issues growing up and still do till this date. I decided to talk to my daughters cf doc (pulmonary) and he then ordered a sweat test. Both results came back borderline, 47 and 49. We are now in the process of ordering a full panel but due to insurance difficulties, the test has not been done. My.question is how likely is it that I indeed have cf? What does borderline results indicate? Thanks for any information you can give/advise.

 

[sweetninis]

@amber682

Your son has one unknown mutation so have u and your partner done your tests which one of you has unknown mutation

 

[Lety]

Hi Steven,

I know I need to be tested again. My excessive appetite and still loosing weight. I eat constantly and have 4 or more bowel movements a day. I don't see any oil but the frequency is alarming to me. My dd is DDF508. I was having some of these symptoms 3 years ago but not as much as now. I do have high liver enzymes. I had the CFTR Full Gene Analysis at Ambry Genetics in 2009. I called Ambry and mention the increase symptoms and they said that there is another test that can be done to look for other mutations. I am very confused about the tests. They mention the Delition Duplication Analysis.

What is the difference between Delition Duplication Analysis test and CFTR Full Gene Analysis?? Could someone tell me in plain english the difference? I went to the website but is hard to understand. I already had the CFTR Full Gene Analysis. Should I have the Delition Duplication Analysis.

I don't know if my insurance covers this test. Could you please tell me how much does it cost and if I can do it directly with Ambry?

Thanks



Thanks

 

[StevenKeiles]

MiahsMom,
We know you have at least one CF mutation, DeltaF508 since your daughter has two of them. It is certainly possible you also have a second mild mutation that explains your elevated sweat tests. It is also possible your symptoms are not related but more of a coincidence.It would certainly be helpful to do a full sequence evalutation to see if you do have a form of CF. Given your history and sweat tests it does sound like a form of atypical CF.

Steve

 

[StevenKeiles]

Lety,
Deletions and duplications are a type of mutation that involve large portions of the gene being missing or duplicated. This involves one or more entire exons. (the CFTR gene has 27 exons) You need to use a different technology to pick up these mutations since they are not detectable using regular sequencing techniques.
this is part of our CF Amplified test, but if someone only had sequencing they couldhave deletion testing performed as we offer this separately as well.
If you have a deltaF508 and a deletion you would most likely have classic CF so if you are atypical or mild it is unlikely the second mutation would be of this type. If you want to be sure you can have the deletion test ordered by your MD.
good luck,
Steve

 

[StevenKeiles]

Daisy,
I agree with your doctors, we do see some carriers with symptoms. It is also possible that you do have a second mutation that we cannot identify. the technology we use to find mutations is able to detect all mutations within the coding regions of the gene. however, mutations in other parts of the gene would not be detectable since nobody is looking there.
Therefore, you do not need to be retested every time a new mutation is identified. It would only be necessary if the technology changed to detected mutations in different places in the gene.
I hope that helps.
Steve

 

[brandonalbert]

Hi,
My son has v520F and the deltaf508 mutations. Was wondering if you had any info on v520F & what class it falls under. Thank you
JHL
Mom to BHL 8 w/cf