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StevenKeiles

New member
ihni,

I would not consider M470V a mutation. The other two mutations listed are considered severe typical CF mutations. In doing IVF if you wanted to only choose embryo's that didn't contain both of those severe mutations that makes sense. You can never predict exactly what would happen but I would not be concerned with a fetus that inherited an M470V since this is actually carried by almost half of the population.

good luck,

Steve
 
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EmmettsMom

New member
I am trying to find out more information about one of my son's mutations" c.365-366insT
Does the "c." mean anything? I checked the Cystic Fibrosis Mutation Database and googled it, but can only find (limited) info when I don't put the "c." in front of the rest of the mutation name.
My son's other mutation is G542X; he has severe PI; sweat test was 84; second sweat test was also in that range. No lung or sinus issues. He's 2.5.
I understand from a previous post that all mutations are rare, except for deltaf508, but is there anything els eyou can tell me about c.365-366insT? I thik I read something that the consequence is a frameshift, and that it's a class I mutation. Is this verifiable? Thanks Steve!
 
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Auntysharn

New member
Auntysharn,

The gene mutation CFTR:c 1408>G(p.Met407Val) is actually not a mutation but a common variant that is carried by almost half the population.

My brother's gene is DF508.
that is the most common CF mutation.

Steve

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Steve thankyou for your reply. So am I interpretting correctly that the combination of the above genes, the common varient + Df508 would NOT cause CF? That the varient is not considered 'disease causing' even combined with a mutant gene?

Thank you very much for you time.
 
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katzyloo

New member
my son was diagnosed after a sweat test result of 75 at 8 weeks old. he presents no symptoms at present. since then the lab has concluded he has two faulty genes, F508 and C2657+2_2657+3insA. Our consultant from the royal sick kids in edinburgh has limited information on the second gene so can not shine much light on it.
i was wondering if someone knows about this gene or even this combination
thank you
katie
 
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JennifersHope

New member
Steve,

I have emailed you before.. I am so hoping my blood got mailed to you today, I have been treated for CF since I was 29 years old, I tested postive via sweat test three times, but I have Addison's disease which can throw a sweat test, I initially had Genyzme test me for 25 mutations and I tested positve for DF508 and no other showed..

Fast forward nine years, I am at a new center, and they are now not positive I have CF since most of my symptoms are asthma related..

Just today I finally had my blood drawn and the test said on it Ambry genetics test Full panel for CF. But I was told it is being sent to the Mayo Clinic, I am going to pass out if that is not you guys... Tell me it is???? PLEASE and if it is not do they do the same thing as you????

Updated, I did call and find out for whatever reason, it goes to Mayo first then it is sent to you, how long is the results going to take and are you doing a full as in complete and nothing left unturned study???

Thanks Steve
 
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jmom

New member
(I posted this in "Families", but thought I'd try here too...hope that's ok.) My daughter is 7 years old. After 5 years of foamy, floating, suspicious looking stool, a positive fat malabsorption test, 3 significant episodes of GI bleeding, 3 colonoscopies with biopsies showing neutrophilic infiltration and lymphoid hyperplasia, as well as a strange lesion in her colon that doctors could not identify, my insurance company (Blue Shield of CA) turned down authorization for an Ambry Amplified genetic test. The basis for their decision was "no family history" and "negative sweat tests". (Sweat tests were 32/33...anyone who knows anything about CF knows that sometimes you can have negative results close to borderline and still have a problem!) I am not an expert, nor am I a doctor, so I by no means presume to know that she has CF on my own account, but why not rule it out so we can move on from here, or deal with it if need be? Hasn't she had enough puzzling symptoms to justify diagnostic testing? Sorry to vent; it's just been a long road...
 
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triples15

Super Moderator
Hi Steve,

Thanks so much for sticking around and answering all of our questions! You're an amazing resource to have around here.

I don't have any specific question but just wondered if you knew anything about one of my mutations. I have one DF508 and the other is S954L. When they found the second mutation a few years ago I believe they told me that so far I was only person documented with this mutation. I could be mistaken though.

I was diagnosed at 3 months old via sweat test, and I'm now 29 and present with pretty classic CF. I've always just wondered about that 2nd mutation out of curiosity.

Thanks!

Autumn
 
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JennifersHope

New member
Me again.. I am so confused, at first I thought for sure my blood was being sent to you because my doctor specifically wrote on there. Ambry genetics. Apparently Mayo does the same test? Do you know if that is true? I want to make sure here that we leave no stone unturned.

I was dx with CF about 10 years ago now, and they are starting to reconsider my dx because I have addison's disease which can cause false postives..

Help
 
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hmw

New member
Mayo's test is not the 'same' although it's similar. According to Mayo's site they won't find 'large deletions and promoter mutations.' What do they mean by promoter mutations? I assume Ambry's test finds those..? <img src="i/expressions/face-icon-small-confused.gif" border="0">
 
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martysmom

New member
Oh I know the answer to this!! The promotor in the thing before Exon 1 in the CFTR. Most amplified tests say that they cannot detect large deletions, deep intronic and promotor mutations. I researched the different kinds of tests when we were trying to find my son's mutations. The CFTR gene has exons and in between each one there are introns and before exon 1 that is called promotor. I hope this helps!! I think (am not positive) that there have only been mutations discovered at the end of introns and not in the middle sections. I could be totally wrong but it might make sense why some people have undiscovered/ undetected mutations.
 
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hmw

New member
Thanks Martymom!

Emily has one unknown mutation so I am always looking for possible reasons why that could be the case. When I asked Steve about it here he explained about the intron mutations (they only look to a certain point) so I have been assuming that is where Emily's 2nd one is (sigh... so wish I could *know* ...at least her 108 sweat test didn't leave anyone guessing on the status of her dx.) And of course we know Ambry looks for deletions, unlike the other places that do sequencing. So to clarify- does Ambry's detect the promoter mutations, even if other sequencing tests do not?
 
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martysmom

New member
I think ambry does check the promoter. Maybe Steve can clarify but I am almost sure they do.
Harriet, I am so sorry that you don't know her other mutation. Did you ever have Emily's blood work sent to sickkids in toronto? Isn't that the place with the database? There is no doubt that she has another mutation and it would be just so fantastic for you guys to just have a name for it. The name provides so much closure!! Maybe they can find it. I think it is amazing how there is this chunk of unknown space that can hold these mutations. WEIRD!! Oh and I saw on another post that Emily is eating well!! CONGRATS!! Maybe she and Marty can join an eating club...LOL!!
Steve, do you have any info. on the CF mutations database and the sickkids hospital in toronto? It seems that there are new mutations being discovered all of the time. When we got our son's mutations report back from quest there was info. on his mutations and sickkids was the reference. Thank you so much!
 
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StevenKeiles

New member
EmmettsMom,

That is a rare mutation, the other name for that one is 359insT. I would expect this to be like a typical CF mutation.

The c. just refers to the cDNA, basically the numbered nucleotides of the gene.

Auntysharn,

Yes you are correct.

Steve
 
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StevenKeiles

New member
Jennifer,

We do receive many samples that are sent through Mayo, so it is possible. Mayo also does a test of their own, so it is also possible that it did not get sent on to us.

Send me the name and sending clinic information to my work email address below and I can follow up for you.

thanks,

Steve
 
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StevenKeiles

New member
To clarify, yes Ambry does check the promoter region which can have some disease causing mutations. The Ambry CF Amplified test checks the entire sequence, including the promoter region, certain intronic mutations and large deletions and duplications. This makes it the most comprehensive CF test available today. It will detect 99% of all mutations which means that there are some mutations that are just not detectable by any test.

The database from Toronto Sickkids is just a list of all mutations that have been identified at least once. It does not often tell you more about the mutation other than it has been seen in someone who may have CF. Sometimes it is not actually that helpful. Many of the mutations Ambry has discovered are listed in the database. We are always working on updating but it just takes time.

thanks everyone.

Steve
 
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StevenKeiles

New member
Autumn,

I am guessing that your second mutation is S945L. If that is your mutation, it has been known for a lot more than a few years so it depends when you were found to carry it. Many mutations that are a little less severe will often present milder and with a later onset. But what you describe is typical with many patients in that symptoms will increase over time and become more so called classic as they get into adulthood.

Hopefully with earlier detection and better treatments this will delay more severe symptoms for more patients going forward.

Steve
 
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