Welcome Ambry Genetics

[mcsimpson]

Steve,
My husband and I just found out that we are both carriers. We are expecting our first child together in Sept. I have the N1303K and he has the R553X. I have been looking for info about these two but not having much luck. If there is anything you could tell me or send me that would be great. I'm not going to have the amnio done so I was just trying to get as much info as possible to be ready if it turns out the baby has it. I know its only a 25% chance but I am still curious.
Thanks again!!
Mary and Nathan

 

[MommyJen]

Hi Steve,
I asked some questions a few years ago when my daughter's pulmonologist decided to have her tested for CF. At that time, they had sent the testing to Genzyme versus Ambry. The results came back negative then. Fast forward three years and the she just spent another lengthy stay in the hospital and they have chosen to repeat the genetic testing. I was told this time it would be sent Ambry. Her pulmologist decided to repeat the testing as he stated new mutations have been discovered since she was last tested. Can you tell me how likely it would be to pick up on something now that wasn't picked up on three years ago? Also, is there some way you would be able to tell me what type of testing was ordered? I would hope that since he feels strongly enough to do this again that he ordered the most complete testing available.

Thanks,
Jen

 

[jonah456]

Hi, Steve. Thank you so much for answering such detailed questions!

We just got the results of our son's Ambry test, and are unsure of what it means. Our doctor has referred us to the local CF clinic for a sweat test and genetic counseling, but we're impatient! I'm hoping you can give us a bit of an explanation...

Our son's results show no 'known mutations' were detected, and no deletions or duplications. He does show 5'UTR-198T>G as a 'variant of unknown significance'.

We've been researching, but still aren't clear on the difference between 'mutation' and 'variant'. (The report has the standard boilerplate that "2% of patients... will have only one mutation detected, so the difference between 'mutation' and 'variant' seems important!) Does his result suggest that he's just a carrier of this mutation? He would have atypical presentation (at 9, his only symptom is pancreatic insufficiency) so does this give further credibility to the theory that he's a symptomatic carrier, rather than actually having CF?

Thank you so much for any light you can shed on this for us!

Lori

 

[makahfili]

Hi steve,

Ok, so the Ambry test came back with:

125G>C (heterozygous), untranslated region. Benign classification.

2694T>T (homozygous), T854T, Benign classification.

Can you help me de-code this and give me some input?! SO concerned! Anything will help!! What exactly does benign mean when dealing with CF mutations? Because my daughter is symptomatic as well as I, however I have not been tested yet. Can you tell me anything about these mutations?

 

[MichelleinKY]

we just got the test results for our daughter and was wondering if you could tell us anything about the combination of deltaf508/c.2789+5g>a we asked her cf doctor and he could not tell us anything about the second gene or what they can or could do together any help would be appreciated
Thanks so much

 

[JaimieC]

Anyone have any idea why the dr hasn't answered any questions in over a month? Is that normal? Just wondering....... I check this thread every day and nothing<img src="i/expressions/face-icon-small-sad.gif" border="0">

 

[Mommy2Zeke]

I know... I've been wondering too.

 

[StevenKeiles]

Sorry about the delay, I have actually been traveling much of the last month at conferences and I am usually notified when a question is posted. I just received notification of the most recent posts, but nothing before that. Maybe it had something to do with the new website. Anyway, give me a little time and I will answer all of the recent questions.

Let's start with the grandson with 3 mutations. Actually it is only two mutations. The M470V is not a mutation, just a common variant that almost half the population has. The other two, deltaF508, everyone already knows, and L467P.
We reported this mutation at last years CF conference and have just had an article accepted for publication that describes this. We have seen this many times, I have not seen this reported anywhere in the literature over the years which is why we published it. This is definitely a disease causing mutation and seems to be associated with fairly typical disease. As with all mutations you can never predict exactly, but I would expect this combination to be similar to those patients with 2 F508 mutations.

Steve

 

[StevenKeiles]

Mary and Nathan,
Congratulations on the pregnancy and best of luck to you both. Those two mutations are typical classic disease causing mutations so if the baby inherited both the risk would be for classic CF. Obviously as I have always said this can be variable from patient to patient, but this would not fall into the atypical or mild category.

Not what you wanted to hear, but one piece of good news is that there are several drugs in clinical trials that target both of these type of mutations so the treatments coming out in the near future look promising for this combination.

Steve

 

[StevenKeiles]

Jen,

Our testing is more comprehensive than what Genzyme is currently offering. There are parts of the gene and certain types of mutations that they will not detect and we will. However, their basic sequencing test will detect the majority of mutations like ours. So yes it is possible we could find something that they didn't test for. Send me the name of your daughter to my private email address and I will let you know more.


Lori,

A variant is called such because it may or may not actually be a disease causing mutation. Until we have more evidence we are unable to say for sure. If it is a disease causing mutation then yes he could be a symptomatic carrier or possibly affected with a second unknown mutation. However, it is also possible that this is just a variant that is not disease causing and he is not even a carrier. As the years move along feel free to contact us at Ambry to see if more information becomes known about this variant.

Steve

 

[StevenKeiles]

Makahfili,

Benign means not disease causing. These are both common vaiants that are seen in the general population and are not associated with disease.

This testing was probably not performed at Ambry because we do not put these type of findings on our reports since they are not significant and only tend to confuse not only patients but sometimes doctors. We do report this information if requested by the ordering physician, but 99% of physicians do not request it. Other labs will often report everything that is found even if not significant, so your test probably went to a different lab.

Steve

 

[StevenKeiles]

JaimeC,

See the answers to Mary and Nathan's post, it is the same type of mutation combination. DeltaF508 and N1303K are both severe type mutations as is the R553X.

Ashley,

Rare mutations do not mean mild. In fact any mutation that ends in an X is typically severe. Given that both are X mutations I would expect a classic CF presentation. I have heard stories like yours many times. The CF carrier test is just a screen, it only picks up about 80% of carriers. Being negative just means you are less likely to be a carrier since the test cannot detect 100%.

Anchored,

Just like I said above most tests are only looking for a set of certain mutations. The Ambry test is always looking at the whole gene so we can pick up not only common mutations but rare mutations regardless of the ethnic backgroud of the individuals. The mutation you mentioned appears to be a more mild mutation, and with only one mutation found it looks to be just a carrier. Hopefully the evaluation with the pulmonologist was helpful for you.

Steve

 

[StevenKeiles]

Jen, (Zekes Mom)
I imagine you have your results by now. Let me know if you have other questions.


For everyone,

Results of tests can take 1 week, 2 weeks or up to 5 weeks. It all depends on what tests were ordered and what lab they went to. When you are doing just a mutation panel they typically take 1-2 weeks.

For Ambry, the 508First part will only take about 5 days, but if we need to do more testing it will take an additional 2-4 weeks on average.

If somehow I missed your question or did not answer something please just post another question. Again I apologize for the delayed responses.

Steve

 

[MichelleinKY]

Was just wondering if you could tell me anything about c.2789+5g>a we have asked our CF doctor but they can't tell us anything about it at all besides it is a rare one if this is true how rare is it and what does it cause. We have been very lucky as of right now with no symptoms besides the salty taste and her feet and hands sweat like no other but other than that she has gained weight going from 7 LB 1 OZ and now she weighs 16 pounds and is 5 1/2 months old any insight would be greatly appreciated

 

[edan]

Hi. we have known our 3 year old has CF for about 2 weeks. She is df508 and 3849 +10kbc->t. To date, no symptoms, but just yesterday cf doc put her on antibiotics based on information from her primary doc because she was complaining of boogers for a few weeks and just had a bloody nose. Although, I don't think she has anything wrong right now.

Based on no symptoms to date and pancreatic sufficiency, can you tell me any more about this combination of genes?

She was diagnosed because we were going to have another baby so they tested both my husband and myself. I then proactively tested her becase we were both found to be carriers. Sweat test came back as 58 so we had the genetics done....

 

[StevenKeiles]

I cannot tell anyone anything about any combination of mutations regarding CF since there is always a wide range of symptoms that can occur. Two siblings with the same mutations won't always have the same level of disease.

Regarding mutation being rare, that is true. All mutations are rare except deltaF508, some are more rare than others.

both the 3849+10kb and 2789+5 are moderate mutations, which can cause anywhere from a more moderate to classic presentation.

Each child needs to be treated independently and based on how they are doing.

Sorry I couldn't be more helpful, but there is no way to predict what will happen with any two mutations.

Steve

 

[kaylinsmom]

Hi, I posted some duestions a couple of months ago and I still am unsure about this. I will try to make this short. My 7 yo has had health issues for about 4 years now, including gi problems, asthma, headaches, recurring pneumonia, fever that comes and goes, a cough, she had swine flu last november and was hospitalized. Anyways, she has had 2 sweat tests and they were 30 and 44. Hey pulm sent blood off for genetics and it came back with one mutation. They told me it was the more thorough test. They also did a fecal test, ct scan of her sinuses, blood work, and sputum test. Which they all came back within the normal range. She takes advair and singulair evryday and albuterol as needed. I am still concerned about that one gene mutation. I have read that some cf carriers can have symptoms but should I make sure she is just a carrier by doing ambry? Since all of the tests they just performed came back normal. We are actually going to her pulm in a couple of hours for a check up and her pft's and they are a cf accredtited place. I really like her docs and trust they are taking care of her but I guess as a mother you never stop worrying. Thanks so much in advance! Well, we are home from the pulm and they have put her on miralax everyday and prevacid. And possibly peractin to pick her appetite up. They also upped her dosage of advair because she is not improving on her asthma. Still coughs when excercising. I cannot stand her being on all of this medicine but she is obviously not healthy. Thanks, Erin

 

[mcsimpson]

Thank you very much!! Its not what I wanted to hear but I would rather be prepared than not!! We will hope for the best!! And for further progress in treatments!!
Thanks again!!

 

[Shameh]

My grandson is 10 weeks old. It took the full genetic test to get results. He has R117H. They called it Atypical Metabolic type. He seems very healthy, good appetite and growing very nicely.

We are not sure what this means and when I try to find info on the internet, the only info I can find would take a degree in genetics to decipher.

Can you please give me some info in plain English. It would be greatly appreciated. What to expect? Treatment?

Blessings in advance

Shameh

 

[mom2caseyafrica]

My DD has the mutations deltaf508 and f508c. From what i've read, in some cases, the f508c mutation has been benign. That was not the case with my daughter. She had pancreatic insufficiency and was put on enzymes. The lack of sweat at 2 months old resulted in no sweat test until 4 months. The numbers came back as 13. They redid her stool sample test. Her pancreas is now working. No more enzymes! And yet she currently has staph. This is all very confusing. =)... I would love to learn anything I can about these 2 mutations... What can you tell me about others experiences with these mutations, what you know about the genetics of these 2 mutations,etc.