Welcome Ambry Genetics

[StevenKeiles]

Jeanne.

We have never seen this mutation so I am unable to provide any additional information at this time. You will just need to see how he does over time since regardless of the mutations there is always variability even in the same mutations.

Steve

 

[StevenKeiles]

ENaC analysis?

Jeannes
Ambry does not offer enac testing and I am not aware of this being done outside of research.

Steve

 

[jmiller]

Hi Steve,

I have two mutations: 2184delA and DF508. Can you tell me which class 2184delA falls into? I have found conflicting answers in my research ranging anywhere from "unknown" to "frameshift, class I" to "Somewhere within I, II, or III". Has this mutation been classified? I am particularly interested in knowing given the information I have learned about the potential of VX770 to help in a couple of different classes.

Jackie

 

[MyBabyCeline]

Hi Steve,

I posted a question just before jeannes post and I would really appreciate it if you have any information that would help me.

Thanks a lot.

 

[KatnAshlee]

G542X (c.1624G>T) ; L671X (c.2012delT) Help single mum plse....

Thanks for your feedback steve.

I have tried doing a lot of reasearch and am finding it difficult to find much information on the second gene L671X (c.2012delT). Could you please advise me how many people in your database have the combination genes as my daughter does, and how many people are regiesterd in your database.

I am keen to find out how common this combination is, because all I seem to find is a large number of people who have the DF508.

Im still waiting for an appointment with our genetics team, and they have told me anywhere from 2-3 months, which is so hard as we have spent half of her life in hospital and she is only 3 months old mainly for weigh issues, and fast resporiatory rate which they can not find any reason for this, as her o2 levels and negetive infection have left them telling me that maybe this is just the way she is, and has her own way of breathing. To me it just cant seem healthly for long periods of time.

Any further information would be so much appreciated.
Thank you!

 

[mom2owen]

Sort of a generic genetics questions:
When you do gene sequencing, do you look at everything that makes up a person's gene by itself or do you compare what that person has in relation to the gene mutations you know about? I am not sure if that makes sense. But, what I wonder about it how you add more mutations to the list of CF and what you mean when you have never seen a mutation before?
And, if a person has a polymorphism, how do you know it isn't disease causing?
Maybe this isn't so simple to answer, just very curious about how it all works. Thanks a lot!

 

[billsmom]

Steve,

My son as the DF508, and 405+1G-A mutation. I can't find much online regarding the second one, except that it is predominantly Jewish and that there was a 20 year old girl in Germany back in 1993 that had the same two mutations, and was doing well. It was a study on a "donor splice" mutation.

Can you please help me understand how this mutation differs from the DF508, and what impact it may have, if any?

Thank you.

 

[valshingle]

Steve,

My 19 yr old daughter was diagnosed at 6 weeks via the newborn screening. Her mutations are DF508 and Q1382X. I can not find much information about the latter mutation. Can you tell me what class of mutation it is and if you have any other people in your database with that mutation? I know of only one other person and that is in France.

She is doing reasonably well, cultures with SA and PA, has chronic sinusitis and had her gallbladder removed. PFT's range from 80-93% and she does have pancreatic insufficiency.

Thank you!

 

[StevenKeiles]

hana,

Sorry I missed your question. I have only seen a couple of patients with that mutation and a form of CF so I really can't make an assessment.

The thing to remember is that all mutations are variable and there is no way to predict how any one combination might present. In addition, even two people with the exact same mutations can have different disease, therefore you have to look at each case individually.

thanks,

Steve

 

[StevenKeiles]

Mom to Bill

It appears that both mutations are classic CF mutations so i would expect a typical CF presentation.

The thing to remember is that all mutations are variable and there is no way to predict how any one combination might present. In addition, even two people with the exact same mutations can have different disease, therefore you have to look at each case individually.


Steve

 

[StevenKeiles]

Jackie,
I am not certain if this has been proven but I have seen it classified as a Class I mutation. It is a frameshift mutation but causes a stop codon further down in the gene from the mutation. that is typical of most frameshift mutations and also explains why most of them are severe.

Steve

 

[StevenKeiles]

G542X (c.1624G>T) ; L671X (c.2012delT) Help single mum plse....

KatnAshlee

We have never seen the L671X mutation but I would expect that combination to be a severe classic presentation since they are both stop codon mutations. Whether or not it has been seen really doesn't matter in that case.

best of luck,

Steve

 

[StevenKeiles]

Valshingle,

I do not know what class it is in, and we only have a couple of other patients with that mutation.

It appears that both mutations are classic CF mutations so i would expect a typical CF presentation.

The thing to remember is that all mutations are variable and there is no way to predict how any one combination might present. In addition, even two people with the exact same mutations can have different disease, therefore you have to look at each case individually.

best of luck,

Steve

 

[StevenKeiles]

Mom2Owen

See answers below,

When you do gene sequencing, do you look at everything that makes up a person's gene by itself or do you compare what that person has in relation to the gene mutations you know about?
We look at the sequence of the patient compared to the normal sequence. Anything that is different from what is normal is reported.

But, what I wonder about it how you add more mutations to the list of CF and what you mean when you have never seen a mutation before?
We are not looking at a list we are looking at the patients DNA so we do not have to have seen a mutation before to find it now. What I mean is that our lab has not detected that mutation and I do not have a patient in our database with that mutation. We are not the only lab in the world who does this testing. We have probably done more than any other lab but we certainly have not seen every mutation that has ever been reported, just most<img src="i/expressions/face-icon-small-happy.gif" border="0">

And, if a person has a polymorphism, how do you know it isn't disease causing?
Based on how frequent it appears in the population as well as studies that have been done on that particular polymorphism.

Steve

 

[AleksandraKaczynska]

Hi

Do you know anything of the mutations my daughter has. I have heard from others with the 3849+10kbC>T and it seem alsways to be the leading mutation and a mild case of cf reflecting mostly on lungs.
But do you know anuthing of someone with 3849+10kbC>T / R533X.
Joanna is doing fine - she has no symptoms however there seem something to be showing on her xray in the bronchi - the doctors however refer to it as not importanat - however due to cf - and say there is no development in the lungs.

Aleksandra

 

[mom2owen]

Thanks Steve! We sure do keep you busy here, don't we? I appreciate your help and time.

 

[MyBabyCeline]

Thank you steve for your feedback.

What do you mean when you say you have seen a couple of patients and "a form of CF"? Do you mean that these patients did not have typical CF symptoms? Or that there were different phenotypes associated with these mutations? Were they mostly mild or severe? And were you talking about the combination of 2183aa>g + F693L or only one of them? If you meant the latter then which one of the mutations were you talking about? 

I completely understand that this disease is variable and that it shows differently in each patient, and that however mild or severe were the cases you've met this might not be the case with my daughter. But I would really appreciate to know what exactly you encountered during your long experience regarding these specific mutations.

Thanks again for all your help, I deeply appreciate all the effort and time you put in answering our questions.

 

[bhm]

New Diagnosis

Steve,

Before my wife and I got prenant, we had genetic panels done on each of us. I came back as a carrier for DeltaF508 but have always been very healthy (i'm a 7min/mile distance runner). My wife had initially reported as negative for CF but has last week was identified as a carrier for 5T12T. We have an 11 month old that's tested negative on a newborn screening, a sweat chloride test (14) and appears to doctors to be free of any symptoms. We are waiting for a genetic panel result on my daughter.

One more thing, my wife is 4 months pregnant.

We're really concerned and wanted to get your opinion on probabilities that either my daughter or our unborn has a significant issue.

 

[kellyga]

Steve,

My daughter is 3, and she was born with meconium illeus. Other than that, she has been relatively healthy. She has one DF508 and one described as c.4197_4198delCT. I can't find it in the databases online. Do have any information on it, what class it is? Any information you have would be appreciated. Thanks.

 

[CJPsMom]

Steve,

This is a very random question, however, is there any research that shows any increased likelihood of passing along CF genes if there are many other recessive genes? For example, are people who are homozygous recessive for hair color, eye color more likely to pass on the recessive CF gene?

Obviously, I'm not a scientist, but am wondering if there's anything that indicates greater chances than 1 in 4 for any possible future pregnancies.