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StevenKeiles

New member
Since you were negative then yes your husband would have to carry the R1162X mutation and yes all three kids could be carriers. Would it be that unusual to flip a coin and get 3 heads in a row, not really.

If there is a question about your son I would just have them do a CF sequencing test to make sure there are no other mutations. And the IRT level does not mean anything, it is either positive or normal. And if it is positive it just means you need more testing and most babies with an elevated IRT are not affected with CF, but some of them do turn out to be carriers.

Steve
 
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mom2my3kids

New member
Steven (Ambry)

Steven,

My son's full panel detected the following:

They say the following: Two alterations, both predicted to be deleterious:
1)A heterozygous deletion of CTT at nucleotide 1653-1655 resulting in an in-frame deletion at codon 508 in exon 10 of the CFTR gene (1653-1655 del CTT, F508del)

2) The 5/7T and 10TG/12TG intron 8 variants were detected.

Two changes from the "normal" or wild type of the CFTR gene were detected inthis sample.

To which you replied implicated mild CF however I am having the hardest time getting the official DX from docs because no one really knows what is going on with my son. I am frustrated and want to know if you have suggestions. UPDATE: xander has lost weight and is now down to 5% rather 25% growth. His poo is runny and stinks to high heaven... it is my understanding that these two symptoms coupled with his coughing and lung problems "looks" like CF but no one will say for sure...any insight?

Thanks for your time
 
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hmw

New member
Hi Steve,
I got the results of my boys' tests.
Timothy came back completely clear- no mutations at all. <img src="">

Shawn came back the same as Emily did- one DF508 mutation. We made plans for additional testing to try and help determine what this means for him, starting w/ another sweat test. (ETA: We did the 2nd test today and it came back at a 54. Next in line: going to a urologist for an U/S looking for 'congenital bilateral absence of the vas deferens'. He is flipping out over this; can't say I blame him!)

Anyway... any input would now be welcome. I so wish we knew that 2nd mutation on my daughter. It would have made all of this so much simpler... *sigh*
 
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thiot2000

New member
Steve,

I received the one page results report and want to clarify that all tests were run. I think we have an all clear...

Here is what is shown on the report:

CFTR FULL GENE Known Mutation: None Detected
Novel Variant: None Detected

CFTR DEL/DUP Gross Deletions/Duplications: None Detected

The "interpretation" states that no mutations, novel variants, deletions or duplications were detected in the CFTR gene. It also states that the results of the deltaF508 revealed no copy of the mutation.

That seem straight forward enough, but then I get to the next page and am reading the fine print and it states that polymorphisms and the poly T status will be reported only upon request. Is that something we need to ask about or are the above results enough to have our 99%+ chance at not being a carrier?

Thanks in advance!
Kim

P.S. The clinic received the report on 2/11/09...so that was a turn around time of 3 weeks from the day the sample was received. I guess it only <i>seemed</i> like months...
 
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StevenKeiles

New member
Steven (Ambry)

Jana,

I would double check the results you listed here with the actualy report and if you are correct, I would ask the lab that ran your test to double check the results because it is very ususual for a deltaF508 not to be on a 9T chromosome. You listed only 5 and 7. Almost all cases of deltaF508 and a 5T also have a 9T that is why we know that when you have both the deltaF508 and the 5T they are on opposite chromosomes and you have a form of CF. In addition, with 12TG repeats the symptoms you describe would be consistent with those findings.

Steve


Kim,

Yes that is as normal a result as one can get and it is 99%.

Steve
 
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hmw

New member
Steve,
In regards to my past questions about how to advise my family members when it came to screening for CF... would it just be best for me to be tested for the F508 mutation? If I turn up positive, we'd know my dh's family is the one with the mystery mutation. (I already wonder that anyway, given his brother has a son with one known and one unknown mutation.)

If I were to turn up with the F508, would a basic screen be sufficient for any family members needing it since this is the most common mutation?
 
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CLEAmom

Guest
Steve-I have learned more reading here today than weeks of study and in advance thank you.
1 child with chronic pancreatitis, 1 with pancreatic insufficiency and severe pulmonary involvement (right now dx as asthma)
Child with pancreatitis results from Ambry: Polymorphisms are M470V,R75Q and 7T/7T Poly T Variant. She is also SPINK positive, but doc did not feel that alone was enough to count for the severity of disease. Nothing else found.
Hospital told us she has CF, but that is confusing to me. They are also very concerned about our other daughter and both have an upcoming appt at the CF center.
Your insights are greatly appreciated since the report stated both polymorphisms are not disease causing and we have 2 symptomatic children.

Thank you again!
 
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StevenKeiles

New member
Harriet,

You are correct that since the deltaF508 is included in all panels a basic screen would be recommneded for everyone in the family who is intested in carrier testing. And it really doesn't matter who carries it in your case since both sides of the family would need to check for all the mutations in the panel anyway.

Steve
 
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Lety

Guest
Steve

Finally I got my results and says that they did a CFTR Full Gene Analysis.

The result

CFTR 508 First delta 508 (Am J hum Genet. 1990; 47.354-359 ) in exon 10 of the CFTR gene.

Is there a posibility that I could have another rare mutation? I have some of the CFers symptoms.


What does it mean ?

Does the full Gene Analysis mean that I'm just a carrier and no other result is possible?

Would you please check your records to see what type of analysis was done? Does this confirm that I'm just a carrier?

I'm also sending these questions offline.

Thanks so much for your help.
 
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beccasmom

New member
HI Steve

This is a little bit of a long story, but need so help. My 2 1/2 year old has since birth had repeated episodes of hypoxia and pnuemonia. She also has recurrent sinusitis and severe GERD. Over year ago she had 2 sweat tests the results were 46, 48. She at the time also had severe failure to thrive, she had a complete arrest of growth for almost a year. She had immeasurable levels of A,D,and K as well as a very low level of Vit E. She was found to be pancreatic insufficient. She had a broncoscopy which the pulmonologist said looked like CF. She had a very extensive series of other tests including a ciliary biopsy that was negative. 15 months ago the doctors decided it was CF. She had an Ambry which showed only a single mutation, I believe it was G542X, it was a known disease causing mutation. Since being treated with enzymes and the vest etc my daughter has done great. SHe is growing, her vitamin levels have normalized and her respiratory issues are much better.

Recently my daughter was hospitalized andd her pulmonlogist wanted to repeat her sweat test for prognistic reasons and because the CFF recommends a repeat sweat test over the age of 2 her other tests had been done prior to age 2. Her latest result is 16 so normal.I am very confused as is her pulmonologist since she clinically appears to have CF, and has responded well to treatment. Do you have any thoughts?
 
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StevenKeiles

New member
Beccasmom,

I believe I had a conversation today with your doctors office. This is an unusual circumstance, I would suggest you follow up with the doctor to see how they want to proceed. I do not want to have an open discussion about someone's case.

Best of luck,

Steve
 
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Munkeesmama

New member
Hi Steve,

We got our one page final reort back for the test.

Under results it states:
Known Mutations: none detected
Novel Variants: none detected
TG Repeat/Poly T VariantL (TG) 12-5T/(TG) 11-7T

Under interpretation it goes on about those repeats and variants. then it says:
"This patient is a carrier of the (TG)12-5T variant in the CFTR gene which could be contributing to the symptoms of this individual. No other mutations or novel varients were detected...You may wish to consider additional testing for CFTR gross gene deletions and duplications which account for 1-2% of CFTR mutations.

So, my questions is, does all this mean she is a carrier of CF, and what other testing should be considered. When the receptionist called she said "The test was negative." didn't mention a need to schedule another appt. or anything. I had her send me the results and now I'm left with more questions.

My daughter is symptomatic as well. Her sweat test results were 19 and 22 at the age of 1.

Can you shine some light on what any of this means in laymen's terms? Thanks!

Edited to add: If this finding does mean anything substantial, would you recommend having our other children tested as well?
 
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Stacia

Guest
Hi Steve,

Just have a question for you, my daughter was just diagnosed a year ago in August. She is now ten years old. She does not have much of the lung problems, just the intestinal part and the horrible sinuses. Everything that I read says that the problems ususally get worse when you reach adolescence, well we are getting close to that. That part of that scares me to death. Can you explain to me why that happens.

We are having a really hard time with her doing treatments. She doesn't want to take her pills, shortcuts her vest treatments, doesn't want to drink her high calorie shakes. I am at the end of my rope trying to figure out what to do with her. I try to tell her what can happen if she doesn't do this stuff. I think she looks at herself as being healthy so why do I have to do this stuff.

Stacia has mutations G542X and 5T variant in combination with 12TG repeats on other number number 7 chromosome. What does that mean and what do you usually see with those for her future.

If you can help me and explain these things to me I would greatly appreciate it.

Thanks,
Susan
 
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saveferris2009

New member
Hey Steve,


Here is a list of the most common CF mutations in the world in 1994, as provided by Canada's Sick Kids Hospital.<a target=_blank class=ftalternatingbarlinklarge href="http://www3.genet.sickkids.on.ca/cftr/resource/Table1.html
">http://www3.genet.sickkids.on..../resource/Table1.html
</a>
Are you aware of any more recent information? Do your company have any by chance?

Thanks!
 
S

StevenKeiles

New member
munkeesmama,

The results mean that yes she is a carrier of a more mild to moderate variant, which is like a mutation. If there is nothing else then it is not worth testing others in the family. However, if there were also a deletion then this could be a form of CF. That is why we recommended considering deletion testing.

Steve
 
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StevenKeiles

New member
Susan,

A combination of the G542X and the 5T/12TG is a form of CF. However, since the 5T is a milder mutation this usually causes a more mild to moderate disease. CF is a chronic disease for everyone. With all chronic diseases they never get better in time they only get worse. Now for some is can be well into adulthood before things get more seriouc. There is no long term evidence and this is just my opinion, but I feel the more you can treat appropriately and prevent or minimize now, the better off she will be as she gets older and the less permanent lung damage she will have when she is in her 40's, 50's and 60's. Of course what makes you think your 10 year old child will listen to you more than any other kid listens to their parent.

I hope this helps. Good luck and by the way, very cute pictures.

Steve
 
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StevenKeiles

New member
To everyone,

Regarding a list of common mutations. There really is no list that has all the mutations and the frequencies. What is posted on the Sickkids database is very old information. We do not have a list at Ambry that is postable. We have all of the mutations that we have seen in our patient database which is searchable, but is not something we are able to post. We use this when we are reporting results or consulting with physicians, nurses and genetic counselors. We have processed over 20,000 samples for cystic fibrosis and yet some mutations we have only seen 1 or 2 times. Therefore, even with a list it is not possible to have exact clinical information attached to each mutation. Unfortunately, there is just a level of uncertainty in all mutations.

I hope that answers some questions and I am sorry i don't have the information you are looking for.

Steve
 
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Munkeesmama

New member
Thanks for answering my question. Is the deletion testing automatically done with the amplified? If not, do you keep samples there, and what do I need to do to have my doctor request the deletion testing? Thanks in advance.
 
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saveferris2009

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

To everyone,



Regarding a list of common mutations. There really is no list that has all the mutations and the frequencies. What is posted on the Sickkids database is very old information. We do not have a list at Ambry that is postable. We have all of the mutations that we have seen in our patient database which is searchable, but is not something we are able to post. We use this when we are reporting results or consulting with physicians, nurses and genetic counselors. We have processed over 20,000 samples for cystic fibrosis and yet some mutations we have only seen 1 or 2 times. Therefore, even with a list it is not possible to have exact clinical information attached to each mutation. Unfortunately, there is just a level of uncertainty in all mutations.



I hope that answers some questions and I am sorry i don't have the information you are looking for.



Steve</end quote>



But the "basic panel" tests for the most common mutations, right? how common are each of those mutations?

Thanks for your help, Steve
 
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