What does 7t, 7t mean? Also, advice on missing school.

[kaylinsmom]

We are still in limbo over my daughters diagnosis. We are waiting for PCD blood work to come back, as the biopsy was unconclusive. But as I was looking over some of the papers the doc handed me, I noticed they had put G576A, 7t,7t. I knew her mutation was G576A but was does the 7t, 7t mean? I have tried to look it up but can not find anything. Thanks for the help!
Also, any advice for what to do when your child misses SO many days of school? My daughter is in gifted and talented 4th grade but I am being questioned about all of her misses. She has missed about 20 days so far this schhol year. They are being nice about it and Kaylin is staying on top of her work but I am wondering about homeschooling?? Just curious as to what others do in this situation. I homeschooled her in 2nd grade because of all the misses and we did fine but she missed it so I sent her back to public school for 3rd and 4th. Thank you for any advice!

 

[Justinsmama]

Hi,

We are in the same boat. My son is in 2nd grade and identified as G&T but without a GIEP (we just agreed on Friday) because of cluster classes and high enrichment. We too are given a hard time about the amount of time he misses (only about 8 this year as opposed to 30 plus last year). This is our first year in public school. I end up sending him when is not feeling well, but not clearly sick. Mostly GI issues and/or just getting a cold. It is a hard position to be in. Is your daughter mostly out for lung issues or GI? Is she pancreatic sufficient? Justin is insufficient and has mostly GI issues and no baseline lung problems but things change very quickly if he has an infection or cold. He has had 6 infections since last Feb, 4 from Feb to April last year. It is so hard to know when to push him to go. He looks pale and tired a lot of the time. He just doesn't feel great. Not a good position to be in when you are 8.

We also have one known mutation and the 7t,7t. I was told the 7t means nothing. We are thinking about doing deleation/duplication testing for the second mutation. Doctor said it would just be for our knowledge.

Josette

 

[Melissa75]

I missed 20+ days each yr of middle school and stayed on top of assignments/got good grades. Unless your daughter is falling behind, i wouldn't pull her out. And if she is falling behind, you don't have to pull her out. The school should work with you.

 

[kaylinsmom]

Thank you for the advice. Josette, Kaylin has mostly lung issues. However, she is on nexium and miralax everyday. Her new complaint is headaches. She is PS although, I am not sure of the test they did to check. I remember taking in a stool sample and they said it came back ok. Thats interesting about the 7t?? If it doesn't mean anything then why do they put it on paper? Weird. Melissa75, thanks! It is hard deciding but she loves school so much. I will talk with the administrative staff and see what they recommend. I know as long as she is staying on top of things they shouldnt do anything but I just hate for her to miss daily lessons taught in class. Thanks again for responding.

 

[kyeev]

There are 3 common variants along exon 9 of CFTR.
They are 5T, 7T and 9T.
The 7T and 9T variants cause no disease and are found in the normal population.
However, the 5T variant is associated with absence of the vas deferens and is most commonly picked up during screening of infertile men.
It causes skipping of exon 9 (coding region 9 of CFTR).
In general, it is thought to cause very mild CF, with the only symptoms being infertility.

 

[cgerhardt]

I have 3 kids and they all have variants. My oldest son has 5t 7t and the older he gets the more lung issues he has. My middle child also has 5t 7t she has respitory problems and takes creon. She was admitted for the first time last year and was in for 5 days and on home ivs for 3 weeks. My youngest has 7t 7t had we were told he wouldn't have any problems. He is 4 and has been admitted 7 times and on home ivs 3 times tested positive for pseudomonas, and another bacteria that is related to pseudomonas, and staph. Our doctor is great and looks at each of my children and thier problems and addresses them and not what the books or research says. We do neb treatments and the vest on all 3.

 

[Justinsmama]

I honestly think that the double 7t's that Justin have may play a part in his eventhough I was told it does not. We are always the exception to the rule.

 

[LittleLab4CF]

I was tested in 2002 for CF by Ambry Genetics. At the time I was shown to have a 7T, 7T Polymorphism at m470v. There were no other poly T alleles. Last year I repeated genetic analysis again by Ambry showing the same polymorphism. A “T” polymorphism is like the “T” key on your computer sticks occasionally and you get a string of “T”‘s. Look at it like a genetic stutter where a Thymine gets repeated several times. A 5T, 5T indicates two or more repeated poly T patterns.
So What? A TR (Trans-membrane Regulator) gene is being read, a template for TR work is being prepared and up we go reading each rung of the DNA ladder when all of a sudden, the next five rungs have to be jumped in order to keep making an accurate template. Starting with (3T or) 5T and higher, the efficiency of our ability to jump that gap goes down. It doesn’t really work exactly like this but for all practical purposes it explains the problem.
What defines CF from the standpoint of genetics is a moving target. Two genetically identical CF patients having nearly everything demographically equal can present contrary symptoms. In other words two nine year old girls from the East Coast tested to be homozygous ( a copy of DDF508 from each parent) DDF508 can have totally different health histories and issues. One may be dealing with severe pulmonary symptoms and the other girl could have less pulmonary problems and much more GI health issues.
Genetics is a hot topic in CF for good reason. CF is a single gene disorder and a genetic mutation of the TR gene becomes a CFTR (Cystic Fibrosis Trans-membrane Regulator) gene mutation. The TR gene was sequenced in the late ‘80’s and as suspected, a series of gene mutations defined the genetic cause. The two most popular mutations were found and some fool assumed we were dealing with peas. Until the last couple of years, most doctors, CF specialists or not, treated CF genetics as if the determinations would be black and white. Being people, our genetics isn’t going to be that easy. Now there are nearly 2000 CF genes that have been looked at beyond mere identification of a mutation. Another 1200 mutations are identified but as yet nobody has determined what if anything they do.
The short answer is; Yes you can have a positive sweat test and fail to be defined as having CF genetically. Since the Gold Standard still remains the sweat test, if genetic analysis says you do not have CF, the genetic interpretation must be wrong. The most current, and a liberal interpretation of CF, says if a person exhibits the symptoms of CF, they have CF for all practical purposes. This may not satisfy a stringent statistical definition but when you are sick, being told what you don’t have isn’t always best.


LL

 

[kyeev]

I honestly think that the double 7t's that Justin have may play a part in his eventhough I was told it does not. We are always the exception to the rule.

I think I didn't explain myself very well.
7T and 9T are polymorphisms (i.e. normal). Everybody in the normal population has either 7T/7T or 7T/9T or 9T/9T.
CF comes into play if you have 5T/7T or 5T/9T.
(Polymorphism means a change in DNA sequence that is not disease causing)
(whereas mutation means a change that is disease causing).

Its also possible to have 5T along one strand of DNA inherited from your father with ANOTHER CF mutation on that same strand.
And then say a different CF mutation along the DNA strand inherited from your mother.
So you could end up with R117H/5T on one strand and DF508 on the other.

Justin more than likely has one known mutation, I'm guessing DF508, and one other uncommon mutation.
The more uncommon the mutation, the less likely it will be picked up by genetic screening.
So they've tried screening for 5T, but thats come back normal as well i.e. 7T/7T.
So, now they'll have to send a sample of to a specialist screening facility that will pick up, say, the top 100 mutations and hope its in there.
And there's still no guarantee they'll find it.

Another common polymorphism that crops up is M470V. This is not disease causing either.
I don't know why they bother screening for it to be honest.
About half the normal population have the M variant and half have the V!

 

[Justinsmama]

Hi,

Justin was diagnosed last Feb. He has one known F1052V. He is PI with a fecal elastase level of 25 when they stopped testing. He had severe malnutrition. They are suggesting testing for duplications/deleations to find his other mutation. Do you know what that means? Does it mean in was not inherited but was a spontanous mutation?

 

[kyeev]

Hi,

Justin was diagnosed last Feb. He has one known F1052V. He is PI with a fecal elastase level of 25 when they stopped testing. He had severe malnutrition. They are suggesting testing for duplications/deleations to find his other mutation. Do you know what that means? Does it mean in was not inherited but was a spontanous mutation?

Just means, he's got a very uncommon mutation on the other DNA strand.
Even F1052V is pretty uncommon, so they've done well to find that one!
(It also seems to be associated with milder CF).

If you're trying to find a very uncommon mutation, and you've tried out all the screens available (say the top 100 mutations), then your next best guess is to go for duplications and deletions because they're relatively easy for a normal screening lab to.
For example DF508 is a very easy mutation to spot using basic screening tools because its missing 3 DNA bases.
So they'll try and find a similar mutation to this.

The next step after this is a full sequence screen where they sequence the entire gene.
This used to be a big deal 5 or 10 years ago (time and cost), but with the new DNA sequencing technologies, its possible to do in an afternoon.
Problem is not many screening facilities have the technology so your doctor would have to search around for somewhere to do it.
Hence go for the easier duplications/deletion screen first.

 

[Justinsmama]

Thank you so much, I did not understand the dup/del before this. My last question (at least for now) is, since F1052V is usually associated with mild presentation and pancreatic sufficiency, we can expect that his other mutation is what causes his PI. His baseline for lung function is around 100% with no cough, but as soon as he gets anything (cold, virus, bacteria) it drops anywhere from 15-30 percent for his FEV and to the 50% for his 25/75 (which tends to be lower than everything else anyways)

Thanks again.

Josette

 

[LittleLab4CF]

Kyeev, and others with a T polymorphism. The origional post begged "what does 7t, 7t mean? A T Polymorphism literally means "many repeated Thymines". A DNA gene contains instructions coded as A's, G's T's and C's. Each letter corresponds to a chemical like "T" for Thymine. The 4 letters each have a mate and two join to make a rung up the DNA staircase. Your TR gene might be going along like; AGTCCGTAATGCC. Let's insert a 5T polymorphism; AGTCCGTTTTTTAATGCC. The 5 extra "t"s are obvious.

I have copied Kyeev's post on mutations and polymorphisms to some fellow researchers. Some of our information is contradictory and I hope Kyeev can PM me with his sources of information. The first post states that the 5T variant is associated with defects in the vas, causing male infertility. In both posts it is clear you hold the position that polymorphisms are harmless (I.e. normal). Should men consider sterility normal?

Anyway I only explained in more detail the genetics of 7t, 7t. When I was tested in 2002, I was told just what Kyeev stated, 7T, 7T polymorphism at m470v is not known to have any effect on the disease course. The mutation S1235R was found as well with the same information. This was disappointing to say the least. Researchers are a cautious lot and to that end we often resort to word play to cover our butts. Instead of stating clearly that the only information available is a lack of contrary information we say things to confuse the issue.

In the repeat of my genetic testing in 2012 they dropped the m470v reference but the results were the same. Five years ago I revisited my abysmal genetic conflict as I had already been confirmed CF via two positive sweat tests. When I got the pea plant genetics version of CF my heart sunk. I confirmed my CF specialist wasn't just trying give me the pedestrian version of CFTR genetics and expressed my doubts about his explanations. I gathered all the research papers and such that supported a broader palette of non homozygous CF mutations etc. and forwarded it on to him. The polymorphism wasn't on my radar at that time and didn't find, nor look that hard for information. Somewhere, sorry I read 30+ scientific abstracts daily, I read about research involving CFTR polymorphisms and disease presentation. This last year I discussed repeating genetic testing.

The first thing was a review of the 2002 test. My doctor brought up the issue of 5T+ polymorphisms stating that the latest data on 5T variants and higher is showing up in CF patients when exhaustive genetic testing has eliminated everything (we know). Ok, that's my couch, maybe there is something still unknown. My 2002 test covered a few hundred anomalies. The 2012 Ambry test was exhaustive, including the 1200 untested mutations. My doctor went on to say that the T polys seem to have remarkable upper respiratory infections. Beyond that the polymorphisms start to wander like other CFTR gene mutations. For now, as sexy as genetic medicine is, the CF patient is best served by the CF specialist who for now must treat using the standard medical arsenal. Just make sure your CF doc keeps current on up and coming genetic drugs.

Again the short is this. Some evidence indicates a CF disease course with 7t, 7t polymorphism. Apparently some evidence (based on Kyeev's contribution) says no. She already has CF so demand she treated as such. Hang the genetic testing for now. When a genetic medicine becomes available, celebrate. Until then, educate yourself on CF genetics because it will become necessary to talk shop with your daughter's medical team.

LL

P.S.
Another genetic term that seems to have a new definition is "mutation". A genetic mutation means a change in the genetic make up of a cell or cells in an organism. Mutations are good, bad or have no effect. A somatic cell in a milk duct can spontaneously mutate and you get cancer. This is not a hereditary mutation although there is another hereditary mutation that properly combined can virtually assure breast cancer. Evolution depends on genetic mutations. For some evolution is up for grabs but to utilize science, evolution must be trusted for practical purposes. This is sophistry, but the CFTR gene mutation supposedly guards against cholera's greater raveges, dehydration. Another more successful gene mutation appeared around 3300yrs ago that does guard part of the population against certain influenzas. The mutation deals with the most lethal human disease of all time save TB.

 

[kyeev]

Kyeev, and others with a T polymorphism. The origional post begged "what does 7t, 7t mean? A T Polymorphism literally means "many repeated Thymines". A DNA gene contains instructions coded as A's, G's T's and C's. Each letter corresponds to a chemical like "T" for Thymine. The 4 letters each have a mate and two join to make a rung up the DNA staircase. Your TR gene might be going along like; AGTCCGTAATGCC. Let's insert a 5T polymorphism; AGTCCGTTTTTTAATGCC. The 5 extra "t"s are obvious.

Sorry, LittleLab, Polymorphism does NOT mean many repeated Thymines. It means change in DNA code that is not disease causing.

I have copied Kyeev's post on mutations and polymorphisms to some fellow researchers. Some of our information is contradictory and I hope Kyeev can PM me with his sources of information. The first post states that the 5T variant is associated with defects in the vas, causing male infertility. In both posts it is clear you hold the position that polymorphisms are harmless (I.e. normal). Should men consider sterility normal?

Separately, 7T, 9T and 5T are indeed strings of Thymidines, along exon 9 which influence exon expression and more importantly skipping of Exon 9 during transcription of the CFTR gene.
7T and 9T are not disease causing (therefore polymorphism) while 5T obviously is disease causing (therefore a mutation, hence the absence of vas def).
Sorry if this was not clear.

Anyway I only explained in more detail the genetics of 7t, 7t. When I was tested in 2002, I was told just what Kyeev stated, 7T, 7T polymorphism at m470v is not known to have any effect on the disease course. The mutation S1235R was found as well with the same information. This was disappointing to say the least. Researchers are a cautious lot and to that end we often resort to word play to cover our butts. Instead of stating clearly that the only information available is a lack of contrary information we say things to confuse the issue.

Next, I think you are a little confused here about M470V. It has nothing to do with 5T/7T/9T (which is along exon 9), as M470V is along exon 10.
M470V has a single base change at position 1540 along the DNA strand, changing A to G, resulting in a change in the amino acid code of CFTR from M to V (hence the M470V).
M470V is most definitly a polymorphism (non disease causing) because you can find it in 50% of the normal population.
A disease causing allele will always be below 1%.

In the repeat of my genetic testing in 2012 they dropped the m470v reference but the results were the same. Five years ago I revisited my abysmal genetic conflict as I had already been confirmed CF via two positive sweat tests. When I got the pea plant genetics version of CF my heart sunk. I confirmed my CF specialist wasn't just trying give me the pedestrian version of CFTR genetics and expressed my doubts about his explanations. I gathered all the research papers and such that supported a broader palette of non homozygous CF mutations etc. and forwarded it on to him. The polymorphism wasn't on my radar at that time and didn't find, nor look that hard for information. Somewhere, sorry I read 30+ scientific abstracts daily, I read about research involving CFTR polymorphisms and disease presentation. This last year I discussed repeating genetic testing.

The first thing was a review of the 2002 test. My doctor brought up the issue of 5T+ polymorphisms stating that the latest data on 5T variants and higher is showing up in CF patients when exhaustive genetic testing has eliminated everything (we know). Ok, that's my couch, maybe there is something still unknown. My 2002 test covered a few hundred anomalies. The 2012 Ambry test was exhaustive, including the 1200 untested mutations. My doctor went on to say that the T polys seem to have remarkable upper respiratory infections. Beyond that the polymorphisms start to wander like other CFTR gene mutations. For now, as sexy as genetic medicine is, the CF patient is best served by the CF specialist who for now must treat using the standard medical arsenal. Just make sure your CF doc keeps current on up and coming genetic drugs.

Again the short is this. Some evidence indicates a CF disease course with 7t, 7t polymorphism. Apparently some evidence (based on Kyeev's contribution) says no. She already has CF so demand she treated as such. Hang the genetic testing for now. When a genetic medicine becomes available, celebrate. Until then, educate yourself on CF genetics because it will become necessary to talk shop with your daughter's medical team.

ARGH! No, no, no! 7T/7T is normal. Get that Doctor to test himself, he will have either 7T/7T or 7T/9T or 9T/9T! I guarantee it!

LL

P.S.
Another genetic term that seems to have a new definition is "mutation". A genetic mutation means a change in the genetic make up of a cell or cells in an organism. Mutations are good, bad or have no effect. A somatic cell in a milk duct can spontaneously mutate and you get cancer. This is not a hereditary mutation although there is another hereditary mutation that properly combined can virtually assure breast cancer. Evolution depends on genetic mutations. For some evolution is up for grabs but to utilize science, evolution must be trusted for practical purposes. This is sophistry, but the CFTR gene mutation supposedly guards against cholera's greater raveges, dehydration. Another more successful gene mutation appeared around 3300yrs ago that does guard part of the population against certain influenzas. The mutation deals with the most lethal human disease of all time save TB.

 

[Jessiesmom]

My daughter had the Ambry Genetics screening done at National Jewish in 2004. Before the test came back the doctors there sent us home with the Vest - told us she definitely had CF based on their 2 week observation of her and sent notes to her doctors here in Florida on how to treat her. Months later the testing came back and all they could find was M470V 7t/7t. The doctor that called me from National Jewish instructed our doctors to continue to treat her for CF since that is how she clinically presented. For the longest time lungs were her biggest issue - always had tummy issues but it wasn't until March of 2012 that she was put on Creon. So ..... does she have a mutation that they didn't know about in 2004? I don't know but know if we didn't treat her for CF the way we do she would be one sick(er) kid!

 

[momofmia]

Hello Parents,

Contact your childrens school and request a 504. Your children will be protected by this. It gives special coto complete homework and tests, home schooling. My daughter has PCD and has been 504'd for years. She missed 40 + days of school her Sophomore year of high school was still on the honor roll!

Lisa
AKA momofmia

 

[kyeev]

My daughter had the Ambry Genetics screening done at National Jewish in 2004. Before the test came back the doctors there sent us home with the Vest - told us she definitely had CF based on their 2 week observation of her and sent notes to her doctors here in Florida on how to treat her. Months later the testing came back and all they could find was M470V 7t/7t. The doctor that called me from National Jewish instructed our doctors to continue to treat her for CF since that is how she clinically presented. For the longest time lungs were her biggest issue - always had tummy issues but it wasn't until March of 2012 that she was put on Creon. So ..... does she have a mutation that they didn't know about in 2004? I don't know but know if we didn't treat her for CF the way we do she would be one sick(er) kid!

In 2004, there were well over 1000 mutations known to cause CF.
So your daughters mutations, whatever they are, are probably in the mutation databases out there, just not routinely tested for.
Routine screening will generally only detect the top 20 mutations, with specialist screening maybe top 100.

So, your daughter's mutations are probably just rare and weren't on the panel of mutations tested for.

They'll need to sequence the whole CFTR sequence to find them.

 

[LittleLab4CF]

Kaylinsmom,
Please accept my sincere apology. I forgot for a while that Kaylin and your challenges keeping her in the best health possible is the crux of your query. Genetics is why we have CF and if something simpler worked to eliminate the underlying problems of CF we most likely would already have them.

For all the encouragement behind genetic testing for CF, it is of no value for but a tiny fraction of those tested. To add insult to injury a lot of people showing CF symptoms find that the gene "polygraph" has determined that someone is lying. I have dealt with this stigma over and over and it belies a basic medical tenant to do no harm.

I am closing on fifty years of being in the field of genetics. And I have enjoyed more rabbit trails, dead ends and failures than most geneticists alive. Two words that sit heavy on science are theory and proof. Theory is harmless as long as it is identified so. When it takes on more than an unproved idea it is harmful. As a scientist I have to deal with the theory of evolution. A sensless battle has erupted between religious genesis and science over the weight of theory so it is important. Proof in genetics requires faith in many indirect measurements. Ferriting out how something like a salt regulating gene works consumed a substantial amount human resources. For our relatively small CF population of 30,000, most of whom have no involvement in CF population disease statistics, anybody including myself correlating anything genetic with certainty of how or if it affects a person is suspect. If Kyeev is as smart as I believe, he knows this too. In fifty years a lot of genetics has been absolutely, completely wrong. I have even enjoyed some fleeting fame only to be unceremoneousely booted off White Rock when my work failed replication elsewhere.

For Kaylin and you maybe the take away from all of the stuff I just made worse is this. When a genetic medicine comes available she will be free of what is wreaking havoc on her body. Direct your doctor to keep Kaylin healthy by all means until then. I fear to predict when that will happen but with at least one drug being successful there is hope it could come soon.
LL

 

[kaylinsmom]

Littlelab, you are obviously very intelligent and I appreciate your comments! Genetics, for me, are very hard to understand. I am learning more and more every day. I am so glad we have this site to help with all of our fears and questions.
Thank you all for taking time out to comment! Any advice is appreciated. The more I can learn, the more I will understand.

 

[kaylinsmom]

Momofmia,

Should I ask the pulmo about this as well? Does the school need something from the doctor to authorize this? Thanks for the info!