Welcome Ambry Genetics

[StevenKeiles]

SSLondon,

I don't have specific numbers but I can tell you that I know of many patients who have presented with atypical symptoms and sweats near 30 who turn out to have a form of CF. If they do have mutations, they are obviously not common classic mutations because they do not have classic disease. I would recommend a full sequence analysis. Then if it is negative you don't have to keep questioning it and if it is possible then you know what you're dealing with.


Best of luck,

Steve

 

[StevenKeiles]

One other point about sweat tests, even though technically a sweat of 30 is normal. I do not think that is normal, to me that is a signifcant level which requires further investigation. In the US, the cutoff recommended by the CFF for newborns is anything over 30 is significant. Now your son was a little older when he had his sweats, however even in adults I think a sweat of 30+ is significant.

Steve

 

[sslondon]

Thanks Steve - this has been going on so long, we just want to know what we are dealing with. Looking at our options on how we can actually get the test you recommended done now...

-Steve

 

[consmom]

Hi, my son has F508 and G542x the docs want to test me to see which gene I carry and which one his Dad carries. I have to admit I am not very up on the genetics of CF but is it worth going to the trouble? They seem to think it would help in tests for other family members.

 

[StevenKeiles]

Consmom,

Normally I would agree it would be helpful to know which mutations come from which side of the family, but that is only when one or both of the mutations is rare. These are two of the most common mutations, so any test by any lab would pick up these two mutations. Therefore family members on both sides should know that CF runs in the family and testing is an option for them. Wherever they get tested would pick these up, so it is really not necessary for the both of you to be tested if you did not want to.

Steve

 

[jaazavala]

<begin quote><i>Originally posted by: <b>StevenKeiles</b></i>







However, like above, many patients with normal or borderline sweats will have one mutation. Some will have two, but when a sweat is very normal, it is very unlikely for us to find two mutations. When the sweats are very high, we almost always find two mutations,



Steve</end quote>

What is a "very normal" sweat number?

My 1yr old daughter had a sweat test that was 10. She also has had an almost constant lung infection for 6 months, including 1 hospitalization, reflux with spitting up blood, abnormal stools, and a constant runny nose.

 

[BabyBeauty]

Steven,

First of all this is wonderful you take the time to answer so many questions! Thank you!

I have a couple for you:

My daughter has DeltaF508 and G542x. Could you tell me what these two mutations present? Or direct me somewhere that could tell me?

I am the carrier for DeltaF508 and have always battled digestive issues - pancreatic divism, ulcerative colitis, and gastritis. Does DeltaF508 carry these symptoms? If so is there such thing as a symptomatic carrier?

Any help would be appreciated!

 

[BonnieD]

Steven, I am a grandma and my two cf kids have been gone for nine and 13 years. They were 29 and 26.

Back in the day we had no idea of what mutations or genes we carried. We worked with Dr. Lieberman in trying to develop a carrier test.

My older daughter may be a carrier and she has two daughters. My older granddaughter is definitely a carrier. What does it cost to do this testing and find out if they are carriers and what mutation. Also they are near Childrens Hospital of Orange County, is that where they would get testing?

Thank you very much....

 

[StevenKeiles]

Ashley,

I would say that any sweat test of less than 15 is a very normal sweat test.

Avery's Mom,

Those are two of the more common CF mutations and are typically associated with classic CF, although not every case of CF is the same and some are definitely milder than others.

Steve

 

[madencanada]

Steve , I was wondering if you could give me info on your genetic testing . Cost ? Procedures ? etc . I live in canada and the process here is really slow . THanks Cheryl

 

[clementinebaby]

I148T

Hello Steve,I have a question specifically regarding the genetic mutation I148T. I am pregnant, and after learning that I am a carrier, my husband was also tested. I tested positive for DelF508, and he for I148T. After being certain that this means a 1/4 chance baby will be positive for CF, I began to do some research and have found numerous reports that I148t only manifests in CF if it is paired with another gene "in cis" or on the same chromosome or something. I read that it is now recommended that if a parent tests positive for I148T mutation, he or she should also be tested for this other gene. So, is this true? From what I have read, I148T is
rarely accompanied by this other allele and so perhaps my husband isn't truly a carrier of a CF causing mutation? I understand that I def. carry a CF mutation, but is baby safe as long as my husband does not carry both I148t and its accompanying allele? sorry if my language is off, genetics is pretty.. new to me. Can you give a rough estimate of how
often I148T has this other gene 'attached'? IF all this is the case, I'd really like my husband to be tested for this other gene before going through with amniocentesis. I hope I have been clear in how i've phrased this, would soo appreciate some info.

 

[holmfamily1992]

Hi Steve,

Just a quick question, Is it common for a certain mutation to be carried on from one family member to another or can mutation's change at some point? Example: I carry the R117H mutation, does that mean that my brothers little girl should be tested for that same mutation or would they just test for all that they can?

Thanks, Tina

 

[StevenKeiles]

madencanada,

We receive samples from all over Canada, so it may be possible to have our tests ordered through your local hospital. Why don't you contact me directly at my contact info below and let me know where you live and what clinic you go to and I can see what may work for you.

Steve

 

[StevenKeiles]

ClementineBaby,

It is correct that the I148T is not a mutation but a common variant, there is ~1% chance that your husband carries another mutation connected to I148T, this mutation is 3199del6. You should check with the lab because it is possible that this was checked after they found the 3199del6. However, if he is negative for this mutation, there is still a chance he can be a carrier because they only did the testing for 23 or so mutations. The likelihood that he is a carrier based on just the panel would be about 1 in 150 to 1 in 240 depending on which panel. If you were to do our CF Amplified test the risks would be reduced to 1 in 2400.

You can contact me directly if you have any other questions.

Steve

 

[Juliet]

Steve, You have the patience of a saint! Thanks for the page after page of education!

What's the difference between a mutation and a variant? I mean they're both changes in the genetic structure on the CFTR gene right? So what about the sequence makes it classify as a mutation vs. a variant? Or is that a term given based on clinical presentation? Might my novel variant ever become a mutation? Or will it be a variant forever? <img src="">

Also why can't you tell if 2 mutations are on the same chromosome or not? And for that matter, how do you tell if someone has 1 or 2 copies of a mutation? Are you looking for something 'normal' in that position and something 'different' in that same position, and if you find that it means it's 1 mutation and 1 normal?

Also, what's the best way to find out which of my 2 mutations and 1 novel variant are linked? I have very mild (not DX till 43) CF, so is it possible my 2 mutations are on the same gene (ie from one parent) and I still have the ability to produce some normal CFTR proteins? I have a daughter with no signs of CF. Both my parents are living. I figure eventually my daughter will be tested (she's 13 now). Would her test definitively confirm which of my mutations / variants are linked? It would have to right? because of the 3 things identified in my test, she obviously inherited 1 gene from me. So if she's got zero or three of the things then that would mean I have all 3 on one gene. Or if she's got one or two then those would be what's linked on me right? (Assuming my husband isn't a carrier, which we don't know for sure.)

Also there are several references in this thread to 5T vs. 7 or 9T. What is that? Is it strictly something associated with the R117H mutation? Or is it shorthand for some other mutation on some other gene? I'm confused. <img src=""> I saw no notation on my Ambry results sheet referring to that, but maybe if it's just associated with R117H (which I don't have) that could explain why.

Thanks in advance! ~Juliet

 

[paysmom]

Steve,
I have a question about 1336K. What class does it fall under and when put together with f508 what symptoms do they cause if any. Is 1336K gene also very rare? Thank you.

 

[StevenKeiles]

Nicole,

I do not know what class it would fall into, but it is not a very common mutation but we have seen several affected people with this mutation. It appears to be a more moderate mutation since most of the patients we have are adults with this mutation.

Patients appear to be pancreatic sufficient, grow various infections and have sinus and lung problems along with some developing pancreatitis.

Best of luck,
Steve

 

[StevenKeiles]

Juliet,

You are correct on just about everything. Testing your daughter would answer the questions of what came from you, unless your husband also happens to carry the deltaF508. Regarding the poly T we only report that when we find a 5T, the 7 or 9 are normal and do not need to be on the report.

A novel variant means that it has not been published in the literature. Basically a mutation means that it would be disease causing, a variant may or not be disease causing and yes over time some variants will change to either a mutation or a polymorphism (non disease causing)

I hope that helps.

Steve

 

[Juliet]

Thanks Steve. ~Juliet

 

[Stannon06]

Steve,

Ou 3 1/2 week old daughter, Ella Kate, was just diagnosed with CF by Childrens Hospital in Birmingham, Alabama. Quite honestly, we were overwhelmed by the information given to us on that day. My first question is one you may want to reply back to me at my private email address.

I was wondering, what is your opinion of this facility? Ella Kate's genetic mutation was DF508/3659delC. The doc was familiar with DF508, but could really elaborate on 3659delC. I understand there are many, many variations of genetic mutations that contribute to CF and that it is impossible for him to know about them all, but I thought we might be better off going to Vanderbilt's CF Center or somewhere the doctors have seen this genetic makeup.

Secondly, does this facility send there lab work to Ambry? If so, what information does that lab work contain?

I will apologize ahead of time for what may be stupid questions, but we are just 72 hrs into our CF journey. We have so much to learn. Here is my email address if you would like to reply there: stananderson70@hotmail.com

Thanks!

Stan / father of Ella Kate (3 1/2 weeks) w/ cf