Anyone with M470V polymorphisms

[jmp1324]

I know this is an older post but my 5 yr old daughter has polymorphism M470 and has had chronic lung findings for 1.5yr (found at checkup) and we have dx of atypical cf. She is on same meds, along with advair, singulair, prevacid. We have had 1 PICC line. She has been on the vest for almost a yr. No pancreatic insuff. We have had 3 neg sweat test (below 10). How is your daughter now? Other than lung findings, cough and poor weight you would not know she was sick.

 

[Julie7]

Ok, well you started jump so I cannot resist replying. I've posted a few times about my 9 year old. He has 2 copies of m470v plus 12TG 5T/11TG 7T and has chronic health issues, both GI (mostly) and lung (mostly sinusitis, bronchitis and pneumonia). He is not dx but followed by CF clinic pulm. We have not seen a genetics counselor yet but I'm really considering it now. I have two younger girls and my youngest is not sickly per se but she's had a persistent cough since birth. She is 1.5 years old. Not sure if CF in family, researching this now but my father has central bronchiectasis (not sure why).
I'm a scientist and generally do not pay attention to anything with a sample size of less than 100. I'm starting to reconsider that and plus, I think we might be able to round up 100 people at this point.

 

[jmp1324]

My daughter had a cough for a few months before her check-up but it was not constant or predictable…didn't pay that much attention to it because there was no other symptom. At the dr visit, they heard wheezing (which we never did). Her breathing was always quiet and clear even the cough was dry but the cough was apparently the 1st sign. I have been told the M470v polymorphism is rare. I reviewed the test results, but do not see any other mutations. Science was never my best subject, so I am doing the best I can to educate myself. It is my understanding that because a person's genetic makeup is so unique, that two people with the same mutations may not present the same way.

 

[Julie7]

How did you get a diagnosis? Glad to hear you have preventative treatments, that's awesome. Yes, I have read the same, that identical twins could have exact same mutations and live different lives, in terms of both quality and length. I think science is only at the beginning of understanding CF and that advances are coming I hope.

 

[jmp1324]

She has a good pediatrician that admits she doesn't know everthing, so referred her to pulmonolgist. We started at shands and after 3 bronchoscopies and no real tx, they did the genetic test but the finding was considered incidental

 

[jmp1324]

And wanted a 4th procedure in 6 mo period…still no tx. I demanded something non-invasive and got breathing med and vest (blessed it was approved) We asked and were permitted a change. I picked all children in st. Pete we just got the dx after they did a bronchoscopy and were shocked by the level of mucus found.

 

[jmp1324]

The pulmonolgist there disccuses with team and did some research. He is going to discuss her case with pulmonologist in the country and see what he can find.

 

[Shellee]

Wow ! I'm so glad to of found this thread I could cry . My 5 year old , Josiah, was diagnosed with cf at 3. He only has two copies of m470v. He is PI as well. He had several pneumonia , 4 sinus surgeries , hospitalized 5 times last year and twice this year for "tune ups"... it's still very hard for Dr's to take me serious which drives me crazy...especially when they consider him mild...we need to get this genotype passes as being disease causing ! Today Josiah just had an EGD...upper endoscopy done by a gi Dr . I recommend this for you all... they found some junk and are sending them off to be biopsied... it's all a much more thorough pancreas enzyme test then the stool test
Feel free to message me anytime!
Shellee

 

[Beccamom]

I am diagnosed with CF with a stop codon 7T M470V and the other gene 5T M470V. I have a healthy child with one M470V7T and a child treated like CF but not diagnosed with my stop codon 7T and 2 M470V variants. She has had sinus surgery recurring pneumonias failure to thrive and is Pancreatic Sufficient. We both culture CF bacteria. I would push for sputum cultures most I portent so antibiotics are based on sensitivities and then I would ask to learn Manuel chest PT while waiting for a vest especially for the kids with bronchiectasis.

 

[jshet]

My son has this mutation. He has had 1 positive and 5 high borderline sweat tests ranging from 55-59. The positive one was 64. He is pancreatic insufficient, takes enzymes, and does 12 hours of feelings through his g tube every day. He is 5ft 5 in. and weighs just 75 pounds. He recently has had a drop in his pft's which if they are still lower than usual at next appointment, he will need treatment.
He also is receiving infusion therapy for severe low bone density.
he is diagnosed with cf, and does all the preventative therapies, vest, breathing treatments, enzymes, sputum cultures at each visit, and the yearly blood draws. He also sees the cf gastro, and the cf endocronolist.
Not everone is the same, this is my sobs situation. He just turned 18.

 

[kyeev]

Wow ! I'm so glad to of found this thread I could cry . My 5 year old , Josiah, was diagnosed with cf at 3. He only has two copies of m470v. He is PI as well. He had several pneumonia , 4 sinus surgeries , hospitalized 5 times last year and twice this year for "tune ups"... it's still very hard for Dr's to take me serious which drives me crazy...especially when they consider him mild...we need to get this genotype passes as being disease causing ! Today Josiah just had an EGD...upper endoscopy done by a gi Dr . I recommend this for you all... they found some junk and are sending them off to be biopsied... it's all a much more thorough pancreas enzyme test then the stool test
Feel free to message me anytime!
Shellee

Guys, I think we have some mis-information here.
M470V is a polymorphism. Polymorphism means "change in genetic code which is not disease causing".
In fact about half the CFTR genes (alleles) we see in general population will have M at position 470 and the other half will have V at position 470.

Similarly, the poly-T repeat in exon 9 of CFTR is non-disease causing if 7T or 9T present, but can cause mild disease if the shorter 5T repeat is present.
So if you have 7T, thats normal. 7T and 9T is what we see in the normal population.

With over 2000 CFTR mutations now documented, at least 1800 being very rare, your problem should be identifying one of these 1800 rare mutations, not following the M470V and 7T red herrings...
Hope this helps!

 

[Victoria Steele]

My son had an entire gene sequencing done, only thing that came up was" The poly T status in intron 8 is 7T/9T and the TG status is 10/11, and p.Met470Val (formerly M470V): An A>G change at nucleotide 1408 in exon 10 of the CF gene led to the substitution of methionine by valine at position 470 of the translated CF protein.
He has clinical presentation. Has cultured PA and MRSA, chronic lung infections, PFTs decreasing annually. We have seen a 30% drop in the last year. 3 borderline sweat tests. Has been on Vest and HyperSal since last November, covered by insurance with no problems, even without a diagnosis. Not PI, but does have other GI issues.
We just switched to a CF clinic for pulmo, and even with the most recent sweat test (yesterday) they are still not completely ruling out the possibility of CF.

For us the M470V IS NOT a red herring, it is ALL we have to go on right now, from a genetic standpoint.

 

[Jessiesmom]

I agree with you Victoria. When you don't have a specific diagnosis the only thing you can do is go with what you've got. My daughter, now 18, has been sick all her life. At 12 they decided it was CF based on an article the Pulmonologist read in a journal. Last year he decided to do another genetic test and it came back negative (but with the M470V 7t/7t) They then retested all her immune system and discovered that her IgG4 is still low (it is supposed to reach adult levels around the age of 10) So we now have a diagnosis not of CF but of IgG4 autoimmune disease and are trying IVIG monthly to help her fight off bacterial infections. Summer is her best time so this winter will be the test.

Just thought I would share a bit of our journey Good luck!

 

[kyeev]

My son had an entire gene sequencing done, only thing that came up was" The poly T status in intron 8 is 7T/9T and the TG status is 10/11, and p.Met470Val (formerly M470V): An A>G change at nucleotide 1408 in exon 10 of the CF gene led to the substitution of methionine by valine at position 470 of the translated CF protein.
He has clinical presentation. Has cultured PA and MRSA, chronic lung infections, PFTs decreasing annually. We have seen a 30% drop in the last year. 3 borderline sweat tests. Has been on Vest and HyperSal since last November, covered by insurance with no problems, even without a diagnosis. Not PI, but does have other GI issues.
We just switched to a CF clinic for pulmo, and even with the most recent sweat test (yesterday) they are still not completely ruling out the possibility of CF.

For us the M470V IS NOT a red herring, it is ALL we have to go on right now, from a genetic standpoint.

Yep, your son definitely sounds like he has CF, but it aint M470V that's causing it, that's one thing I'm sure of.
I'm a geneticist!

It is rare for a full sequence to show up nothing.
Are you sure they "sequenced" or "scanned" or "screened"? Big difference in terminology.
They've possibly missed the mutations during sequencing or the mutations are within the promoter boundary of the gene, which are not normally sequenced. Could also be a hyper rare miRNA mutation.
Sequencing the CF gene may not pick up all the disease causing mutations: http://www.ncbi.nlm.nih.gov/pubmed/23555973