Welcome Ambry Genetics

mom2lillian

New member
Steve

I was wonderging if you woudl be able to provide me with the number of individuals who have been diagnosed with the mutation of P67L, does ambry keep track of such things? I am one of them and I have teamed up with another gentleman who's daugther was recently diagnosed. He has formed a website specifically for those with our mutation which is the 4th identified dominant mild mutation per a small paper published in 1998, it accounts for 1.4% of scottish mutations and 0.2% overall. We have been trolling all over the internet for members and are now having an abstract presented by one of the top UK doctors at the CF conference in Anaheim CA about our website. Our goals can be seen in the abstract which I have included below. I was hoping that by contacting you I could get some sort of estimate of how many individuals we might have out there. Since it is rare I am sure ther are a good number more that are undiagnosed adults running around out there like I was 6 years ago but there are also more babies being diagnosed lately when the doctors do a genetic follow up to a borderline sweat test.

Thanks very much for any help you can supply.



TITLE: WWW.P67L.COM: PATIENT DRIVEN COMMUNITIES IN RARE CYSTIC FIBROSIS MUTATIONS


AUTHORS (LAST NAME, FIRST NAME): Marshall, Tom 1; Hodge, Peter 2; Cunningham, Steve 1 INSTITUTIONS (ALL): 1. Respiratory and Sleep Medicine, Royal Hospital for Sick Children, Edinburgh, United Kingdom.
2. P67L.com Community, Fort Lauderdale, FL, USA.

ABSTRACT BODY: BACKGROUND:
Continued developed in the detection of CF mutations combined with a rollout of newborn screening is leading to the detection of groups of patients who form a very small subset of the total number of CF cases.
If a CF clinic has one of these patients they will generally have no baseline for comparison and in general published series are small. A group of patients with one of these rare mutations, P67L (0.2% incidence worldwide of CF patients), has self formed into a community which can share information about diagnosis, treatment and prognosis.
The aim of the community is to allow these patients to share information in such a way that could potentially benefit themselves and their treating physicians through the sharing of knowledge that may be specific to their mutation. P67L is a mutation found in CF across the world, but more frequently found in patients with Scottish ancestry.
METHODS:
The internet provides the perfect medium for connecting a disparate group such as individuals with a rare mutation. In April of 2007 one parent created a website called www.p67L.com and using shareware was able to create a forum style website very quickly and at little cost.
Word was spread by posting on several health related bulleten boards looking for other people with P67L and also the metatags on the website were adjusted to increase it's positioning in a google search.The forum was set up as a closed website meaning that it is password protected so that search engines cannot get 'inside'. Access to the forum has to be requested through the administrator who vets out applicants first to ensure they have a valid reason for wanting into the forum.
RESULTS:
Within three weeks of being created the forum had 7 patients or caregivers in active discussion ranging from ages 18 months up to 39 years and located in US, Canada, UK and Ireland. Although prognostic conclusions are difficult draw from relatively small patient numbers, there are some interesting information from those already in the
group: Pancreatitis seems to have occured in a three patients, but only in their teens and two patients have had their gallbladder removed.
DISCUSSION:
The P67L.com community is already providing support to parents and patients with this rare mutation. It is hoped that the internet system will enable patients to better understand the symptoms they may experience. We would warmly welcome clinicians inviting their patients with P67L to join the community of patients and parents at P67L.com
 

StevenKeiles

New member
Nicole,

Well this certianly not that rare of a mutation. We have about 35 patients that have CF with P67L as one mutation and another mutation as well. Of course most of the others are deltaF508 as the other mutation, but there are also a number where the second mutation is rare as well.

For Ambry to have seen this mutation that many times this would make it a mutation that we see more frequently. There are many mutations we have only seen once or twice with a lot of others that have only shown up 3,4,or 5 times.

That is a very interesting project you have going. Good luck with it.

Steve
 

annonymous

New member
Hi Steve,
In understand that research is now showing that there are carriers who exhibit minor cf symptoms. My spouse and child can occasionally have salty sweat, so much that it can leave a slight salty frosting behind their hairline or in their sideburns. No one else in the world would ever notice, it's not even "crystals", but it's definitely salt from their sweat. We've had the full ambry done and we know that they are carriers, but there is absolutely no other symptoms to speak of in either of them. Very healthy in fact. But I can't help but wonder if this is something to be concerned about, or can we write it off as "symptomatic carriers" or something. Are we just salty people (maybe more so because of being carriers) or should we be doing preventative treatments, just in case? This has even happened to me before, but not nearly as often as with my spouse or child.

Thanks for any info you might have!
MDC
 

Ratatosk

Administrator
Staff member
A friend of mine's child has health issues, is being treated for an immune disorder. They have yet to get a clear diagnosis -- treating it as if he has CF. Also has sinus infections (has had 5 surgeries), loose stools, wheezing, fevers, high blood sugar... They've tested for several disorders -- one of the tests came back with the following:

5'UTR-142C>A in the promoter region of the CFTR gene

Curious as to whether this is a CF variant, actual cf or has nothing to do with CF....
 

StevenKeiles

New member
MDC,

I would agree that some CF carriers can exhibit some mild symptoms of CF. There are probably other things that interact with the CF mutation to make is more significant. Some people probably have these other factors and some don't, that is why some have symptoms and some don't.

Typically those that do have symptoms, may just have one or two and they usually are milder than what is seen in CF.

This is my take on CF carriers.

I hope that helps.

Steve
 

StevenKeiles

New member
This is a rare variant, that we have only seen one time. So at this point we really don't know if this variant is a disease causing mutation or just a non disease causing variant.

sorry we couldn't be more helpful.


steve
 

grsswspr

New member
Hi Steve,
My wife spoke with a CF doctor today and he said that a person with cf will have the characteristics of the milder gene. Do you know if this is a rule or just a chance.
 

StevenKeiles

New member
Sheila's Dad,

I don't know if I would word it that way, However, I would agree that you need two severe mutations to have a severe disease. In addition, with one or two milder mutations you will most likely have milder disease.

Steve
 
M

momofone

Guest
Hi Steve,

I have been lurking on this board trying to patiently wait for my sons test results to come back. It has been 3 weeks.
Can you tell me anything. Can you also tell me if they ordered the CF Amplified test?

Thanks.

Edit: I sent you a PM

Thanks for the tip Julie
 

julie

New member
Momofone, just a word of caution.... I'd PM this information to Steve. The internet is a very scary place and I'd hate to see someone get ahold of your info and use it for the wrong reason. Maybe you can converse via PM with Steve about this. I know he's been very helpful to me personally in the past. At the very least I'd remove the DOB.
 

ChaufferMom1

New member
Steve;
My questions has to do with PI/ My daughter developed first Amylase def then Lipase def. AFTER becoming a teen. I have read multiple sources about children having PI(especially Amylase) and OUTGROWING it by age 3 or 4 due to an undeveloped pancreas at birth, but I can find no reference to teens developing it. (Especially with no family history or drug or alchohol use). My daughter has a GI appointment in 2 weeks and I am trying to arm myself with info this time. She has had 3 sweat test with results from 11 (most resent and only on the arm for 10 minutes) to 38, NONE are done at an accredited center (we only have an afilliate center here) her sweat test was done at the hospital. the 11 test only took 10 minutes from start to finish....makes me wonder from all I have read. So the question is, from what I have read, some with PI for Amylase only test positive for CF and some negative for CF, I will do cartwheels for negative, BUT, how many...if you know......developed symptoms after their teen years and were STILL negative for CF???? (Both Sweat and Genetic?) We had to change insuranse companies due to work, and I am dealing with MANY other family health issues right now, so I am following each as best I can...but this is very important too. Thanks SOOoooooo Much for your time
Debbie
 

dramamama

New member
Hi Steve-
Wow. I have never been on this thread before. You are so helpful, patient and knowledgeable!! Thank you so much for helping all of us.

I am 34 and just recently found out my mutations...deltaF508/621+1G>T. Never wanted to know them before because if they were "bad" which I guess they are, I did not want it to play into my emotional well-being in dealing with my illness.

Just wondering, now that I know, would you mind giving me any info on the 621+1G>T.... I don't know any info on it....

Thanks in advance for any help you can give.
mandy
 

StevenKeiles

New member
Momofone,

check your private message.

Debbie,

There is a lot of variability with all CF, so it is really difficult to try to guess the likelihood of the outcome. Unfortunately, you just have to wait for the evaluation and all the tests to come back.

Good luck.

Mandy,

As I said to Debbie, even the same mutations can cause different disease in different individuals. The 621+1 mutation is a typical mutation that can cause typical CF. Now what is typical CF, obviously it varies from person to person, but it could include all the major complications associated with CF.

Good luck to you too.

Steve
 

Ninar

New member
Hi I am sorry I am new here and I am not sure where to ask this question. My son who is almost 27 went to the urologist on an unrelated matter and it seems that he has a narrowed vas deferens and they tested him for cf he has a single copy of 5T Allele. What does this mean? I am a nurse but when I studied they had not yet identified the marker. I know that I could be a carrier as I had a first cousin that had cf, I could not find any traces of it in my husbands family. So I guess one of my questions is could he have this from just me or is my husband a carrier? Should I have my younger son tested?
 

janddburke

New member
Steve, I just want to start off by sayingI've learned SOOO much just by reading these posts. thank you so much for all your time and expertise.

I have a question.
we have a 12 year old w/cf. she has mutations W1282X(from me) and R117H (from her dad), she's been doing really well.

my question however has to do with my 6 year old. when I was pregnant I had an amnio that showed the R117H mutation only. Needless to say we were thrilled. we could deal with her only being a carrier.

Lately, after reviewing other posts on this board, I dug out the CF Poly(T) Variant analysis completed by Genzyme.

it states 'Mutation results Negative/R117H
Intron 8 poly(T) variant results: 5T and 7T
The sample provided has one copy of the 5T variant and one copy of the R117H mutation. Based on parental analysis the 5T variant is associated with the R117h mutation identified in the father.'

she had had alot of problems with allergies and asthma. after reading other posts on this board I'm wondering if we shouldn't be treating her for CF?

could her mutation R117H and the 5T variant be considered 'atypical CF' (whatever that means?)

any and all assistance or insight would be gratefully appreciated.

thanks.
 

Fullahope

New member
Steve, my name is Sharon and my 16 yr old son's results just came back
P750L
R1066C

Can you tell me a little about these are they rare, more serious, what may we be looking at long term. I believe he's Atypical based on little symptoms none the less he has CF. Just searching for any and all information on these so I'm informed.

Thanks.
 

StevenKeiles

New member
Sorry I have been unavailable for most of the last week. My wife and I just had a baby. Lillian Jacqueline Keiles was born June 4, 6lbs 14 oz. Both mom and baby are doing well.

So now I can catch up with some of the questions.

Ninar,

First I would want to know what kind of CF test did your son have. If he had only a panel, I would recommend a full sequence test. Most men with absence of the vas deferens have more than one CF mutation that would not be detected in a panel test. If he did have sequencing and only has a 5T, it could have come from either side of the family. Your other son can be tested at any time but if he is not having health problems or children at this time, there is no urgency in testing.

jandddburke,

Since the r117H and 5T are on the same chromosome, she is just a carrier. However, as you have probably noticed, there are some CF carriers that can have some mild symptoms. It is possible that she is more likely to have some of these issues. You can discuss it with her doctors, but it is not exactly CF.


Sharon,

Both mutations are rare but not the rarest. Remember, besides deltaF508 all mutations are rare. The R1066C is a more severe mutation, P750L can go either way. It is difficult to predict the exact future, certainly he could do very well. but it is also possible that more problems could arise at any time.

Good luck,


Steve
 

Fullahope

New member
CONGRATULATIONS Steve on the birth of your baby girl......., how exciting.

Thank you for the information, I appreciate your help very much.

Do you know if there is anyone with my son's exact mutations? R1066C and P750L? I know there is really no way to predict how he will do long term, but I would be very interested to know if someone has these same mutations and if so how they are doing, is there anyway to track that? Just wondering and trying to remain hopeful and strong, this is so hard and scary and shocking for me.

If you can help, great if not thanks anyway.

Sharon
 

StevenKeiles

New member
Thanks,

I have only one patient with that exact combo and I am guessing it is your 16 yo son (from Northern California) Even if we did have other patients with that exact combination, each person could have a different disease severity. If he is doing well up to now, that is good. Of course things could change over time but as long as you are aware and doing everything you can, that is all you an do.

Good luck Sharon,


Steve
 
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