Welcome Ambry Genetics

[LouLou]

Steve, We got the results on Isaac. You might recall my post quoted below. Since I have cf I pushed for sequencing to hopefully close the book on any chance of Isaac having cf. He were optimistic regarding the results when we heard his sweat results of a 12 on both arms. Well he has my G551D and S1235R. Both of us have submitted blood to be sequenced to see if S1235R is indeed from hubby or if it a 3rd mutation of mine.

I read that you hadn't heard of many people with a normal sweat but two mutations so I wanted to inform you of our situation. Also, I wanted to ask you a question. I'm reading that S1235R when paired with a more classic cf mutation such as the one I passed on to him - G551D - will likely result in mild lung involvement, pancreas SUFFICIENCY and pancreatitis. I wondered what you knew about S1235R?

They've found his vas deferens present, passed newborn screening test, no abnormal pancreas stuff and no lung involvement so with the sweat normal and the only cf finding of the two mutations he doesn't fit the cf consortium's cf definition. We are calling it a-typical cf though and am having him followed by CHOP.

<begin quote><i>Originally posted by: <b>LouLou</b></i>

Steven, I am 28 with cf (DF508 & G551D) and delivered a healthy baby boy in July. My husband tested negative for 89 mut's through Genzyme in '04. Recently, I contacted Hospital of the Univ. of Penn's genetics department to get things rolling for cf testing since we can't be sure that our son doesn't have cf with only having tested my husband for 89 mutations. They told me that they used to use Ambry but now use Genzyme that now Genzyme tests for just as many. I've heard you mention Quest being just as conclusive but is Genzyme also now up to par? Please comment.

 

[jenlevy33]

Hi Steve- I finally got the genetic testing back on our son after about 9 weeks. The conclusion was that he is a complex Carrier. He carries Delta 508 & R17OH.
I searched everywhere to find out about this gene but found nothing. They said it was Benign. Also the doctor says that even though he is a Carrier the Cystic Fibrosis Center would probably like to check him out. Do they usually do that? Thanks in advance for your help. Jeanette

 

[StevenKeiles]

Lauren,

The S1235R is a more mild mutation. Many people who have this and one classic mutation will have normal or borderline sweats and those who develop problems will usually be mild as you stated. It is important to remember that many of these problems that do develop may not happen until later in childhood or in many cases even adulthood. Be aware of the symptoms that can happen but realize they may not happen for many years in the future. (not a bad thing).

Jeanette

The R170H is a mild mutation that in combination with another mutation usually results in either just CBAVD (male infertility) or mild pulmonary symptoms. Not a bad idea to have him checked out and followed accordingly. If no problems ever develop, then great, but if something does show then at least you are prepared.

Good luck to both of you.

Steve

 

[Darinsmom]

Hi Steve,

I think you missed my question I postedit was on newborn screening and what exactly is IRT level enzyme? I thought they tested for some of the most common mutations. His IRT level was normal and said they don't do any further testing.
I do have a son with with CF. Thanks.

Laurie

 

[StevenKeiles]

Laurie,

IRT concentrations are high in the blood of babies with CF. All newborn screening starts by measuring the IRT level in the newborn bloodspot. Each state has different testing paradigms and cutoffs, but only the highest few percentage of patients each day are considered positive. Typically if the first test is below the cutoff, it is considered negative and no more testing is done. If it is positive it is either repeated at 2 weeks or sent off for a mutation panel test. So most babies will never get passed the first IRT since it will be negative.

I hope that answers your questions.

Steve

 

[Darinsmom]

Thanks Steve,
what do you mean by cutoff? So since my sons was normal we can be satisfied ith that? Sorry for more questions.

Laurie

 

[Ronda]

Thank you, Steve. You have been very helpful

 

[StevenKeiles]

thanks Ronda,

Laurie,

Each state has a specific value that is their cutoff. Patient samples that are below the number or cutoff are considered normal, values that are greater than the cutoff are considered positive and go to the next step of screening which differs from state to state.

A normal IRT is good.

Steve

 

[Darinsmom]

Thank you very much Steve.

Laurie

 

[TonyaH]

Hi Steve,

I have enjoyed reading all of the these posts and find them very informative. Overwhelming, but informative!

I am asking about my son's mutations, not because I am trying to "predict" his prognosis, but because I am curious!

He has DF508 and 1138insG. Can you please tell me how to understand the second? Is it 1138 with an extra guanine inserted? What class of mutation would this make it? I appreciate any info you might have.
Thank you!

 

[StevenKeiles]

Tonya,

I have never seen a patient with that mutation, so it is definitely very rare. You are correct, it is an insertion of G at position 1138. I would expect this to be a classic or typical CF causing mutation.

Best of luck,

Steve

 

[Luke08]

Hello,

Our son had a meconium plug at birth which he passed after 31 hours. He has had digestive problems (constipation, & diagnosed GERD). He was just diagnosed with diabetes type 1 on Nov 20, 2007. He had a sweat test done when he was a few months old and it was negative. I have mentioned to his pediatrician and his specialists (endocrynologist & his doctor of integrative medicine) about having the Ambry test done and I get nowhere. No one knows what I'm even talking about. We live in Tucson, Arizona and have United Healthcare. How do I get this done??

 

[StevenKeiles]

Luke,

Email or call me privately and I will work it out with you.

Steve

 

[Twogreatkids]

Hi Steve, boy I see you are a busy resource on this site! I have a very similar question as Luke08. The story is too long to tell, but the bottom line is that I want my son tested for the full panel. He has been tested for 99 mutations with no mutations found, but had one borderline sweat test. It was done at a non CF center, so I pushed for a second test to be conducted at an accredited center at the other end of our state. It was 17.....but the tech dropped the "cover" on the collection thingy and so I have these lingering doubts that I can't trust that answer. All the docs there dismissed that he could possibly have CF, and he has been diagnosed with asthma and allergies. Well, he is 6 now and is starting to complain of stomach aches all the time. I have had it with my local ped. so have him scheduled with a pediatric G.I. to get to the bottom of this. Anyway, I want to go armed with info, and want to push for a full panel. How do I find out if my insurance will cover such an expensive test? I have Missouri Blue Choice, sometimes referred to as Blue Cross Blue Shield, and most recently as Anthem Blue Choice. If I can get this doctor to order the test, how do we do it? Like Luke08, all the docs I have asked to date about the full panel test have no idea what I am talking about, and say things like "oh, they can only do that in research hospitals". I appreciate any and all info you can provide. Thanks. Donna.

 

[Morgan0706]

Steve,

I am trying to get some information on my 10 week old son's mutations. He is Deltaf508/1717-1G>A (which I know is a splicing gene). I am just trying to understand all of this. It is quite overwelming. He was diagnosed through an amnio at 28 weeks, so we had a little time to do some research on CF before he was born. He is being followed by the CF clinic in St Petersburg, FL. He is pancreatic insufficient, although he is in the 95% for his weight. I am not trying to predict his prognosis (which looks like we have class 1 or class 2 mutations)....I just would like to get your input and kind of know what we will be faced with. I have learned so much by reading your responses.

Thanks in advance.
Michelle~ mother of Morgan 11, Madison 6 (no cf) & Grayson 10 weeks w cf

 

[StevenKeiles]

Donna,

We have an insurance preverification form on our website if you want us to check your insurance for you. We are contracted with Blue Cross and Blue Shield so I don't anticipate any problems. If you want more specifics regarding getting the test ordered, it is probably better to call me directly.

Steve

 

[StevenKeiles]

Michelle,

Congratulations on the birth of your son Grayson, I can certainly imagine having a newborn in addition to a 6 and 11 year old how tired you must be right now. Just a reminder that it is ok to take a nap during the day if you can swing it.

Anyway, as you probably have learned there is much variability even with siblings who have the same mutations. Both of these mutations are considered typical CF mutations, so I would expect a fairly typical presentation and course. However, that being said not everyone with this combination will have the same disease.

Best of luck,

Steve

 

[badjaw]

Hi steve

i dont know if you will find my sons case interesting, but i would like you expert advise. my son was diagnosed with milk allergies and possibly came down with a virus at the same time. he went thru the ER and almost died. he had severe dehyd. vitiman k level was high. liver and kidneys were not working. they tested him for cancer, rsv, blood disorders, menigitis, ect. and tested everything twice. the last resort was cf bc i was neg. when pregnant my husband neg, and heel pric. neg. they sent his blood again for the new born screening for all diseases including cf and it was neg. so they performed two sweat tests that were in the 40s. they then decided to send the blood to california for full gentic testing which they said would take 4-6wks. that came back neg. he has had 5 or 6 elastays test and the numbers keep moving up, now the test is 195 and above 200 is normal.
he is gaining weight and vitiman blood levels are normal. i have blue cross blue shield of western new york and they have paid for every test so far. we are going to the lung center for a third sweat test dec 18th and my son is only 6 months old.
i supposedly have the best team of cf doctors on the east coast.
what do i do , may i call ambry genetics myself to get an explaination?
bobbie

 

[StevenKeiles]

It sounds like it is not CF, unfortunately it looks like they are not really sure what the cause is as this time. If you would like to call me, feel free.

Steve

 

[badjaw]

thank you for replying Steve, i just found out my test was the genetic deplection/sequencing test? but it was done through quest diagnostics.
They believe he has cf but are waiting for a third sweat test. If it is positive than he does but if is gray area we will do more testing. they say he carries two new mutations and he is atypical, but the hard part will be not knowing what strands he carries. the docs say if its cf his case may be very rare??

i will keep you posed again thank you