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mom2my3kids
08-06-2012, 11:03 AM
My daughter's full gene squencing came back...but its confusing...

A little history is that we had a son (Xander) pass away at 14 months due to CF complications (he had DF508 and a 5t 12tg variant) we assumed since my daughter has shown CF ish symptoms hers would be the same (same parents) but they aren't...

Here is what hers says :

Two alterations:
(1) Positive, predicted to be deleterious: A heterozygous deletion of CTT at nucleotides 1653 to 1655 resulting
in an in-frame deletion of phenylalanine at codon 508 in the CFTR gene (c.1653_1655 delCTT; p.Phe508del).
(2) Variant of uncertain significance: A heterozygous change from G to A at nucleotide 356 resulting in a
change from arginine to glutamine at codon 75 in the CFTR gene (c.356 G>A; p.Arg75Gln).
This individual was found to have 7/9 poly T's and 10/11 poly TG's in intron 8 (non-pathogenic)

Two changes from the “normal” or wild type sequence of the CFTR gene were detected in this sample.

Any ideas as to what this means? I knew if hers read like baby Xander's then sorta I knew what to expect but no idea here...and we dont see her CF doc for 3 more weeks so any insight would be most helpful...thank you

Jana

Jana
08-06-2012, 02:42 PM
Sorry I can't help you with this. My second mutation is a strange one also and includes the G > A business, but the numbers are different, and I really don't know what the codes mean. May I just say, though--you have a beautiful name!

mom2my3kids
08-06-2012, 04:05 PM
:) why thank you Jana as do you...LOL...hoping someone can help with this

2005CFmom
08-06-2012, 09:39 PM
Jana,

I don't know the answer, but you could repost this in the Family forum under Ambry Genetics (it is a sticky topic at the top of the page). Steve from Ambry comes onto the site an answers genetic testing questions.

Allansarmy
08-08-2012, 09:02 AM
I do know that even if you have two children with the same mutation it does not mean that they will have the same health condition. I have always been told that mutations do not necessary mean that "this person has CF worse or better than the next person". I know its not the answer your looking for. Are you asking mainly because of the new medication Kalydeco? Or are you looking for an answer to whether you should be worried? Well, you can't live life like that for sure. You can't always wonder what if my daughter has the same gene sequence and what if her life is also cut short.... can't live in the "What if"

GenH
08-22-2012, 11:37 AM
Hi Jana,

I hope this info helps...

Your son- CF causing gene (F508del) and a variation in intron 8 that can cause atypical cf (5T-12TG).
Your daughter- CF causing gene (F508del) and a gene called R75Q. CFTR2 suggests this alone is not likely to cause CF. http://www.cftr2.org/mutation.php?view=general&mutation_id=92 She also has two different variations in intron 8. It is hard to say how the two genes will interact. Has she had a sweat test?

Each person has two copies of the CFTR gene, so it is likely that one parent has F508del/normal and the other parent has R75Q/5T-12TG intron 8 variation. Your son got F508del from one parent and the 5T-12TG intron 8 variation from the other. Your daughter got F508del from one parent, and R75Q from the other.

There is a lot of variation within intron 8 in our population. You can have 5, 7 or 9 Ts (5 is more severe) and 10, 11 or 12 TGs (sometimes also more or less). This influences how the gene is spliced, which basically means how often the correct protein is made.

I am unsure whether your son had 1 or 2 copies of 5T and 12TG. My following explanation will assume it is 1. Your daughter has 7 Ts on one gene and 9 on the other. She has 10 TGs on one gene and 11 on the other.

Each parent has 2 copies, so two possible options for the Ts and TGs. So there are 4 total of each that could be passed to the child. We know there is a 5T, 7T and 9T making up 3/4 of the parent genes. We also know there is a 10TG, 11TG and 12TG making up 3/4 of the parent genes.

I hope this makes sense. It is more complex now that they can test for the Ts and TGs at intron 8, so it is not just as simple as two mutations influencing the CF diagnosis.

This is a good article, it explains intron 8 and exon 9 on page 475: http://www.colorado.edu/MCDB/MCDB4600/1ReviewPhenotype.pdf

fel
05-06-2013, 07:39 AM
Hi -- I know this is an old post, but.... Does anyone know the full name of the article GenH recommended? It is not on the link. I am trying to understand the very complex CFTR genetics.

Thanks,
Fel

GenH
05-08-2013, 02:19 AM
Hmm I'll try to find it, I see the link doesn't work anymore

GenH
05-08-2013, 08:17 AM
The link I added was a pdf file on the university's website that does not seem to exist anymore. I searched the website and I could not find it.

This link has some useful information, but does not explain the Ts and TGs in detail. Hopefully I'll come across another link that explains this well: https://www.cftrscience.com/pdfs/Primer_Update.pdf

GenH
05-08-2013, 08:22 AM
Some info about splicing and the Ts here: http://www.hopkinsmedicine.org/cfgenotyping/5t%20CARD%20Final.pdf

mom2my3kids
09-22-2015, 04:29 PM
Just to update this post...my daughter is displaying more symptoms digestively than before. I am frustrated because her bowel symptoms match her deceased brother but yet no doctor will say yes or no. I just need answers. Ideas?

jana

Printer
10-12-2015, 07:50 AM
I would suggest that you Google Steven D. Freedman, MD, PhD. He is at the Beth Israel Deaconess Medical Center in Boston. In his practice there he only sees adults but he does see children one day a month at the Boston Children's Hospital.

It is my opinion that there is nobody better dealing with the subject of digestive issues, with CF Patients, than Steve. I would caution you that, digestive issues in CF Patients COULD lead to Pancreatitis and complete pancreatic insufficency..

Bill

zaj1139
10-12-2015, 10:20 AM
My Grandson has Delta F508 and C16796>A (R560K) and 1706A>G (Y569C) He is pancreatic insufficient, has chronic infections, hip dysplasia, etc. My daughter and I are still unclear what it means when you have 3!

Ratatosk
10-12-2015, 11:07 AM
I think there were a couple individuals who've had three mutations. Hopefully your grandson is going to an accredited cf clinic and is being treated accordingly for those symptoms.