Welcome Ambry Genetics

[StevenKeiles]

Angie,

Some patients who are only carriers may exhibit some mild CF like symptoms, so it could be related to that. It is also possible there is another mutation in the family that could cause mild disease. If there is a suspicion by the doctors they can always orde the ambry test on your other daughter.

Steve

 

[ktsmom]

Steve -

Thank you SO MUCH for the information and especially the very detailed response to our Question #2 - regarding having my dad tested for the 508 mutation. I had to shake my head, as your response is exactly what we've been trying to get people in our family to understand, but to no avail, and now no one wants to even discuss "carrier testing" with us. Perhaps this will provide further opportunities for us to have these important conversations with family members.

Thanks again.

 

[agm]

Steve, once again, thank you for answering my question!

I have just one more question:

My son has CF, and when he was tested, only one mutation was found so far, df508. the other is undetected, and being tested now. My husband and myself were tested to see who had what mutation. I carry df508, his was undetected.

Now, my question is, my Mother in Law had a basic panel done (same as my husband and my sons' initial test), her carrier testing has concluded negative, that she is not a carrier. Now, being that my husbands' mutation is not detected on the same panel, would hers have shown anything for being a carrier. She says there is no way she is the carrier. (?) Anyhow, for moral purposes, for the extended family's benefit, it is important for us all to know which side the mutation came from. Would her panel test have been accurate, or should she wait and retest when we know (eventually) WHICH mutation is on my husband's side?

Once again...thanks!

Angie

 

[StevenKeiles]

Dana,

You can send them copies of these emails if it will help. You are very welcome and good luck,

Angie,

You should wait and see what mutation your son carries in addition to the 508. More than likely you are correct, he carries a mutation that is not on the panel so not only your husband but everyone in his family would be negative on the same panel. The only way to know for sure would be to identify the mutation in your son, then confirm that your husband carries the same mutation. Then you would be able to test family members to see who also carries the mutation, but they would probably need a special test because his other mutation is not one that is on any panel tests.

Steve

 

[mbarloewen]

Dear Steven,

I have just read through this thread and wanted to say thank you to you for all the wonderful information.

My wife and I have a daughter who was recently diagnosed with CF after being born with a meconium illeous issue at birth.

We just learned through genetic testing that she carries the delta F 508 gene (which we've found significant information on) and the mutation called 182 deletion T (which I can find little information on)

I understand how symptoms and severity vary from patient to patient but I would very much appreciate any insight you can give me on this particular combination of mutations and any information at all on the typical symptoms of the 182 deletion T mutation.

Thanks for all the information you have already provided,

Mike Barloewen

 

[elle]

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

Elle,



I need to know more about the exact name of the mutation. The way you have it written in not correct. If you have a copy of the results that would be more helpful. Feel free to fax me the report and I can take a look at it. I am not able to figure out what mutation based on how you have it written.



sorry,



steve</end quote>

Ok, thanks anyway Steve. I did check again and the doctor told me that was definitely the name written down. It was also noted on the report that is was a recognised mutation. I am in Australia but I assume that the names of the mutations would be the same internationally (?!). We have a meeting with a geneticist in a few weeks so maybe I can find out more then. It is a shame, I just want to find out all I can about this particular mutation she has. I will post again if I find out more or a different name. Thanks again.

Elle

 

[StevenKeiles]

Elle,

That is not the standard way to document a mutation, so I am not really sure what they mean. Thr1176 means codon 1176 which codes for threonine, so that would be noted as T1176 and then followed by the letter of the new amino acid, but not by two letters. F is for phenylalanine which is not possible unless there are two mutation in that codon. (a codon is 3 base pairs). The S is for serine which is possible, so it could be T1176S. If that is the case, then I have never seen that mutation before. In fact the only known mutation in codon 1176 is 3659delC.

I would meet with the geneticist and see what they say based on looking at the original report. If anyone there has questions, feel free to refer them to me.

Good luck,

Steve

 

[StevenKeiles]

Mike,

It always depends on the combination of both mutations. As a rule you must have two severe mutations to cause more classic CF. However, even with two severe mutations, you may still have mild disease. When there is at least one milder mutation then it is very unlikely to have severe disease. Since there is always variability it is difficult to predict exactly any one situation.

The 182delT is a very rare mutation, so I don't have a lot of information to add. However, this is a small deletion, which causes a reading frameshift. Frameshift mutations almost always lead to a premature termination of the protein which are considered more typical or severe mutations.

Therefore if I had to guess, I would think this combination could result in CF that is anywhere along the normal spectrum from moderate to severe. However, since every case is different you need to treat your daughter accordingly based on how well she is doing. I am sure the CF center you are going to will take good care of her.

Congratulations on the birth of your daughter and good luck.

Steve

 

[mbarloewen]

Hi Steven,

I was afraid you were going to say that about the 182delT mutation, as I noted what you said about deletion mutations earlier in the thread. I can't thank you enough for taking the time to share what you know.

We are being referred into Children's in Los Angeles (we are in Encino) so if you have any words of wisdom to share about this CF center, please don't hesitate to PM me.

Again, thanks for the time you have taken in this thread, it has helped someone completely oblivious to CF just a month ago, to understand quite a bit more.

Mike Barloewen

 

[elle]

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

Elle,



That is not the standard way to document a mutation, so I am not really sure what they mean. Thr1176 means codon 1176 which codes for threonine, so that would be noted as T1176 and then followed by the letter of the new amino acid, but not by two letters. F is for phenylalanine which is not possible unless there are two mutation in that codon. (a codon is 3 base pairs). The S is for serine which is possible, so it could be T1176S. If that is the case, then I have never seen that mutation before. In fact the only known mutation in codon 1176 is 3659delC.



I would meet with the geneticist and see what they say based on looking at the original report. If anyone there has questions, feel free to refer them to me.



Good luck,



Steve</end quote>

Thanks again Steve. I will definitely find out what is meant by the 'fs'. By your explanation, it seems that the mutation is T1176 (and then whatever the new amino acid is). Given that she has one DeltaF508 mutation and the other involving threonine, can you tell me anything about likely severity (even though I understand that it is not black and white) of CF with her? Does the second mutation involving threonine mean that her digestive system would likely be affected the most? Could it mean that her lungs <u>may not</u> be as severely affected as if she was homozygous DeltaF508? I am trying to learn more about the genetics of CF and my knowledge is only very basic at the moment so I'm sorry if I don't make sense at any stage<img src="i/expressions/face-icon-small-blush.gif" border="0"> I know it may seem a little pointless to ask questions about what may or may not happen when there is certainly no clear-cut answer but I just wanted an idea of what these mutations could possibly mean for her. Thanks so very much for your time. I am so happy to have someone to ask who might be able to shed even a little light on this for me.

Thanks again,

Elle

 

[StevenKeiles]

Mike,

I speak the doctors at Children's Hospital all the time. You will be in very good hands. In fact you can tell Dr. Margetis I said Hi.

Good luck,

Steve

 

[StevenKeiles]

Elle,

It is most likely a very rare mutation, so we really won't be able to say much without having more experience. However, even if it were to turn out to be a severe mutation, that still does not allow us to assume it will be a severe disease in that person. Some people with two severe mutations are more mildly affected.

I know no one likes to hear this, but only time will tell how well (or how badly) someone will do from the disease. Of course the good news is that , there is always hope that it won't be too bad.

I am curious to know more about the mutation, so let me know what you find out.

good luck,

steve

 

[pyt722]

Steve,
I am new here and have some questions. My husband and i are both carrier of cf which i know leaves us with a 1 in 4 chance of passing CF on to a baby. I have our mutations and i was wondering if i gave them to you if you could tell me the possible severity or CF if our baby would have it. mine is 3849+10kbC>T and my husbands is W1282X. I am just looking for some information before i meet with the genetic counselor. If you can help me that would be great.

Kari

 

[grsswspr]

Steve,
My brother just got his Ambry test back and it shows that he is a carrier of V754M(same parents). I am a carrier of S492F and my wife is Df508. I was wondering if you have any insight about this (V754M) mutation.
Thanks.

 

[StevenKeiles]

Kari,

The W1282X is a typical CF mutation. The good news is the 3849+10kb mutation is often associated with a milder disease. There is always variability with all mutations, but it is very possible this combination will result in a more moderate disease. Of course only time will tell.

Good luck,

steve

 

[StevenKeiles]

The V754M appears to be a more mild mutation and even if it paired with a more severe mutation, it would likely only cause a very mild disease and it would be very unlikely to have severe disease. If fact some people may have little or no symptoms, while others may have more significant problems.

Hope that helps.

Steve

 

[JDsmom]

Steve, my son has DeltaF508 and R347P (class IV). The only thing I know about class IV mutations is that patients are often pancreatic sufficient (and my son is). Do you have any insight about this specific mutation? Thank you.

 

[StevenKeiles]

JD's Mom,

This mutation is a little milder of a mutation. However, there is always variability with all mutations. I would expect him to do a little better than someone who had two deltaF508 mutations. But there is really no way to predict for anyone. Only time will tell.

good luck,

Steve

 

[heatherrose415]

Hi Steve, Ive just read the last 6 pages and you are GREAT!!!

I have no idea if you can answer my questions but thought I could give it a shot.

My sons sweat test was taken in two different "watches" because he didnt sweat enough the first time. His results came back as 44. A few months later they did a Pancreatic Function Test because his stool studies showed he was malabsorbing carbs and fats. It showed he is Pancreatic Insufficient. His pancreas doesnt release the amylase enzyme. His weight is below the charts, and his height is at 10%. Tomorrow we are gettiing the genetic testing done.

Do you know what his chances are of having CF? He hasnt had any lung issues but is always congested.

I would greatly appreciate your reply!
Thanks,
Heather

 

[heatherrose415]

One more thing, Ive heard of CF patients having "urogenital deformities", not sure what that means. But my son has a dimple in his testicles, could that be related???

-Heather