Welcome Ambry Genetics

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StevenKeiles

New member
Rare mutation

SarahProcter said:
Steve,

When my daughter turned up with the mutation S1159P back in 2008, hers was the only time Ambry had seen it. Has there been any other sighting of it in your tests in the last 4 years? I don't ask for you to tell me anything at all about who or what the results were, but it would be very interesting to know simply if there was anyone else at all found with that mutation, or if Ambry has still only ever seen it once.

Thanks much.
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Sara,

Only one other person with that mutation besides your daughter, no real information to share. All this tells us is that this mutation is very rare but there is no way to predict anything about it. Your daughter will be the best predicter of what will happen.

best of luck to you and to her.

Steve
 
E

EmHug86

Guest
Hi!

My husband is 30 years old and was originally diagnosed with CF when he was 10 years old. He was then tested for his mutations around the age of 18 (he thinks). His results back then (not sure what company did them) was DF508 and unknown. We just re-did these tests through the CFF/John Hopkins. We got the results back today over the phone. We are still DF508 and an unknown mutation per the CF clinic coordinator. I requested an actually copy of the paper work they received back, but it will be about a month before we go for clinic visit. So, what exactly does this mean or entail for the future with all the drug therapies?

I have tried to research having an unknown mutation, and I feel a bit lost.......I can't find much about them. The clinic just told us "unknown." So, does that mean there is not even a name for whatever the mutation is?

Thanks,
Emily
 
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TomMonger

New member
Hello...

I'm a 48 y/o male with severe pancreatic insufficiency, CBAVD, elevated sweat test (59 mmol), bullous emphysema (mainly caused by smoking years before my diagnosis, but haven't smoked in 10 years).

My doc had a full DNA sequence done and it show a Delta F508 and a 5T. I am assuming the "5T" is the allele of the other gene, which is NOT mutated? There was no mention of any other defect.

Can you tell me anything about this combination?

Thanks!
 
P

Printer

Active member
When I was first tested in the late 90's they tested for 250 mutations. In 2011, when I was restesd, I was tested for almost 2000 mutations.

97 is an unbelievable small sample and I would consider it worthless. Of course he can have two mutations outside of the 97 that were tested.

You need to be seen at an APPROVED CF CENTER by a CF SPECIALIST.

Bill
 
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kaylinsmom

Member
Hi Steve, is there anything you can tell me about G576A? My daughter had a full panel test and that was the one mutation they found 2 years ago. Her sweat test was 44. Do you know if there have been any knew mutations found in the last couple of years? Just curious if the test should be done again. Thanks so much!
 
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GlennyB

New member
Hi Steve, I maybe asking in the wrong place. I have a 4 yr old with cf, delta f508 & delta i507. We are in nz. My daughter has severe pancreatic issues, type I diabetes, and recurrent complex DIOS. She has this year had a MACE surgery in attempt to combat the DIOS. Is the answer in genetics? Have you any info, or are you able to point me in the right direction? Thanks in advance.
 
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yellow

New member
My son has one common and one uncommon (actually I havent seen any of that uncommon one here in the forum :S ).

I know how hard it is to be in the middle and be waiting on the result hoping it is not CF.. hang in there, patience and good luck!
 
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LittleLab4CF

Super Moderator
Welcome Ambry Genetics!
TomMonger, This year I repeated my genetic analysis from 2002 w/Ambry both times. The first test covered less than 300 just guessing whereas this test had ten times as many gene mutations. The results were the same and new data were included when describing my mutations. I was diagnosed via sweat test in 2001 but genetically a carrier just a year later. A sweat test or a number of recurring CF symptoms severe enough to be considered a CF patient. 5T polymorphisms and higher like a 7T or 7T, 7T and so on now falls within the CF umbrella. A polymorphism with regards to genetics is a repeated A,G,T,or C once or periodically along the DNA chain that comprise the TR gene. Another very important issue with CF genetic analysis has to do with familiar words from primary education and those are heterozygous (one copy) and homozygous (both copies). DF508 homozygous puts one undoubtedly CF genetically. 7T,7T polymorphism can be either. If you or your baby is caught up in many repeat CF issues, just count on periodically repeating the salt test. Chances are fair she will come up positive in time.

One thing I was especially pleased at Ambry's report was supplying specific research information on a mutation that I might never find on my own. Again it supports the evidence that homozygous mutations aren't the only CF presentation. In my case it is s1235r. I don't know if this is my CF center or Ambry but for such fantastic data, it always looks like a copy of a copy of an old fax. A PDF file would be nice and can be resized for a little larger print. My experience places them a top ally to the CF and (formerly) idiiopathic pancreatic disease.
LL
 
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Gibson75

Guest
Hi Steve,
Just a couple of quick questions. Is there a link between negative sweat test results to any particular mutations? Also, do you know if a full sequence at PALMS RNSH in Australia test for as many mutations as Quest and Ambry do?
Thanks
Bec
 
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LittleLab4CF

Super Moderator
Osteogenesis Imperfecta is very, very rare. I know a woman in her early thirties with it and was friends with her parents when she was born. Ashley was born with every bone in her body broken. As a young lady, her bones were so fragile her fingers would visibly bend depressing a key on a computer keyboard and she always had a cast somewhere. OI babies rarely survive birth and rarer yet is to see an adult withOI. It is so specific in its genetics that even coming from different races, they look like siblings. Now I know two adult women with OI and the could be twins. They sound the same and look five years old from five on.

Both women are happy, educated professionals with a knowledge pain that few will ever share.

LL
 
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AleksandraKaczynska

New member
Well - I have contact with a parent of a girl with both - cf and OI - born with it - not comming from lack of witamins and minerals. They are looking for someone to share experience with as it is, like you wrote - extremely rare.
So if anyone knows of such a person - we would be gratefull for contact.
 
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jmp1324

Guest
Crms

I was wondering if there was any research on sequence variant C1408A>G,p Met 470val (two copies). My dd had genetic testing and it was determined clinically insignificant but now we are facing a diagnosis of CRMS. I know that everyone can present different, even with the same mutation, but any information would be helpful.

Does a diagnosis of CRMS mean the patient will develop CF or is there a possibility that they will not get the CF dx?
Is CRMS progressive like CF?

Joanne
 
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fel

Guest
Hi Steve from Ambry,

I am hoping you can help me understand the genetics of my family -- I had two sons dxed with CF in early April.

Both had positive sweat chlorides (initial sweat test 70 and 76, second sweat test a bit lower in each boy, but still on average across arms over 60) They are ages 17 and 14. The 14 year old was tested owing to sinusitis/nasal polyps. The 17-year old has had a dry cough for over a year, but was only tested when brother came out positive. Neither have ever had serious respiratory issues, but both have asthma, and the younger one had more serious asthma as a preschooler (requiring neb treatments). They both have in tact Vas Deferens. Both boys have been tested for other explanations for having a high sweat chloride (e.g. hypothyroid), and this has been ruled out. Their FEV's are in the 80's to 90's.

I (their mother) have a history of unexplained respiratory issues, sinus issues, and adenoid surgery. I am excellent athletic condition but over the past two years have had breathing issues with exertion. I have a sweat chloride of 37 37. Their bio father/my husband does not desire being tested, but is completely asymptomatic.

Both boys had a full genetic sequence from labcorp. I had a full sequence from Ambry. The boys were dxed with CF based on their sweat chloride, and I have been treated like I have CF since April.

Here's the weird part.
My genetics came up with a potentially benign variant: S912L and a bunch of polymorphisms. No CF. Yet I am responding very well to neb treatments with saline, and my fev's shot up by 20 points.
Older son came up with w1282 and a bunch of polymorphisms.
Younger son came up with S912L and a bunch of polymorphisms.

To me the genetics do not add up. Even if I had a secret allele that was not found in your sequence, I could have only donated it to older son, but not younger son, because I gave younger son S912L. Furthermore, for younger son to have the high sweat chloride and symptoms, he would need another mutation from his father that somehow was not caught in his sequencing, because younger son does not have that w1282. But, if my husband had an unsequenced disease causing gene, along with his w1282, he should be sick. My husband is in excellent health, in his 50's with no respiratory issues, and fine fertility.

Is there some way to explain this data? It seems to me there are only three possibilities:
A. Both boys are carriers but for some alternative reason have high sweat chloride.
or
B. Both my husband and I carry genes that were not caught in a full sequence -- but for some reason my husband's version does not make him sick even along side of w1282
or
C. the common polymorphisms somehow add up to interfering with sweat chloride in my sons.

Thoughts?

Thanks,
Fel
 
R

Rima

New member
Blog

Dear Alyssa - what is the address to read your blog please?
I'm wondering if somewhere out there on the www, there is a list of the 1400+ mutations and what the most common symptoms are that relate to those mutations AND the geographic origin of those mutations....I"d be very grateful if anyone could point me in the right direction.
Thank you
Rima

Alyssa said:
My kids mutations are pretty common, but they do have two of them and they do have A-typical, mild variant CF -- (read my blog for more details)

Now, if a doctor was to look at:
sweat tests
chest x-ray
sinus CT
elastase test
throat swab

They would all look normal in my kids too. (yes, all of these have been done)

But, yes, I'd have to say it's not a guarantee that you son has CF, but they tested for 97 genes, and there are 1400, so chances are with the positive sweat test and that many unchecked genes and mild symptoms (I'm assuming the GI doc suspected CF for some sort of reason) it is not outside the realm of possibility that he does in fact have CF.

Having said that -- there was another post not long ago, that someone posted some really good information about when a person can get a false positive on a sweat test -- you might try searching the archives here.

Best wishes -- keep us posted on what happens.
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S

StevenKeiles

New member
Sorry that I have not been getting notifications when questions are posted to this thread. hopefully that has been fixed and I should be available to answer questions in a reasonable time. If someone still has questions that need an answer please let me know, otherwise I should be able to answer new questions as they arise.

thanks everyone,

steve
 
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Imogene

Administrator
Welcome Back Steve!
I know is at least one member who is a genetic counselor with CF. Maybe she'll "weigh in" too!
Salt and Light,
Jeanne
 
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