Gene Mutations

[SEANP]

Just joined this is my first post so be gentle.  My son has CF
(6 years old). I have always understood that the gene had to be
passed from both parents for CF to express itself. (although now
there have been some studies that have shown that carriers, only
one gene, can late in life express some symptoms).  I
once had a doctor who referred to something like a spontaneous
mutation.  A mutation that is not passed from the parents, but
appears at conception.  Has anyone else heard of this or is he
crazy?  I have not read anywhere else that this is possible.
 Just curious. 

 

[Seana30]

SeanP,

I do not know the answer to your question, but I just wanted to say WELCOME TO THE SITE!

Seana

 

[HairGirl]

Sorry I don't have an answer either. But Welcome<img src="i/expressions/face-icon-small-smile.gif" border="0">

 

[Emily65Roses]

Sean, welcome!

I've never heard of a specific case like that, but it's not out of the question, I don't think. New mutations are popping up all the time. How do new mutations pop up? Some just appear along the way. That's why there are so many more than there used to be (that and they know more about it now, so they can discover a hell of a lot more than they used to).

Thing is, like I said, I've never heard of a case like that. In my head, with what I've heard, I think it makes the most sense that carriers get the spontaneous mutation at conception. Because they don't know, it doesn't make a difference, and then their kids get it from them, like we always see.

Why are you asking? Do you or your wife, to your knowledge, not carry the CF gene? It may just be a really rare one.

<b>Edited to add:</b> Mind you, this is just my theory. I didn't get it from any sources, so don't take my word for it. Haha. I was just thinking outloud, trying to figure how that might work. <img src="i/expressions/face-icon-small-smile.gif" border="0">

 

[JazzysMom]

I havent actually heard of it, but Emilys thinking out loud sounds practical to me! OMG I am thinking like Emily....LOL! BTW WELCOME!

 

[candiebar76]

In our current quest to get the facts because our son has been tenatively dx at 6 yrs old I spoke with a CF dr. I had a million questions about CF, but because they have not confirmed CF w/ DNA test (gets the 36 s.m. panel tomorrow) we can not be sent to him yet (insurance thing). Any way as I was speaking with the Dr. I asked him if the parents are not carriers and there is no family history (we don't know if we carry) can the child still have it? The Dr. said they are exploring the possibility of a "freak" gene mutation that occurs from generation to generation because there are to many families that are saying what we are there is no history. The genes change over time and that is why so much is left unexplained. An example I use is me. We have no family history of twins ever! Yet 3 of my pregnancies were with twins. Granted I lost the twin durring the 2nd trimester w/ all 3, but the Dr.'s said I had the mutation and it is likely that we will now start to see twins in our family starting with my generation. Really wierd stuff I know, but anything can happen. We are only human and it is not up to us.

 

[Emily65Roses]

Just a note:
Not carrying any genes would be a "freak" mutation, yes. No family history doesn't really mean anything. That tends to be a huge misconception. Many of us are the first and/or only CFers in our families. I have a big family. My dad had a sister (who had 3 kids), my mom was one of 6. They all have 2-4 kids each. I am still the ONLY one with CF.

 

[littledebbie]

Oh Emily we have soo much in common.  My Mom is one of six as
well and her Dad was one of six and My Dad in one of three and i
have a sister and a ship load of cousins second cousins even
possibly some kissing cousins..wait I digress....i am the lucky
ducky...the lone ranger...the Mutant member of the family...and
cute too.<br>
<br>
editing to add: sorry i got off topic in your thread..my bad.
 uhmm I know so little about genes it's an embarrassment to my
CF community <img src="i/expressions/face-icon-small-wink.gif" border="0"> But spontaneous mutations sound suspect to me and I
agree the no family history thing doesn't play for me either.
 Particularly since it is such a caucasian disease.  If
it was more of a spontaneous thing would more races be affected?
 Maybe not like I said i am gene ignorant. <img src="i/expressions/face-icon-small-happy.gif" border="0"><br>
<br>
editing again: Welcome to the site!

 

[kayleesgrandma]

Welcome, welcome to the place to be if you have questions. And answers. And comments--ooh we luv comments! Sorry, don't know about your question though--sounds freaky.

 

[anonymous]

spontaneous mutations to create cystic fibrosis are HIGHLY unlikely. The human genome sequence is about 3000 million letters long and most of that is just nonsense, i.e. it doesn't even code for genes and therefore proteins. In fact the 30 000 genes or more only account for roughly 1.5% of the entire sequence. The double delta508 mutation most of us have to create CF is a fault in only ONE of those letters...just the one...how unlucky, especially considering the chances of this muation occuring in a gene. (my rough maths would have the odds of a mutation occuring in the CFTR gene at: 0.00005% though don't quote me on it i'm not a maths person hehe.)

The delta508 mutation has probably been around for 15 000 years, or so i've read, nut its definately thousands of years. This mutations has therefore had a long time to spread throughout the population to the 1 in 25 we see now. This mutation probably survied and was not eliminated by natural selection as being a carrier is thought to be an advantage to the person preventing diorrhea and the such in harsh times of our ancestors. I'm not sure about the other mutations but i'm sure they have been around a long time (maybe not as long to account for there decreased prevalance).

Anyway the point is, it is HIGHLY unlikey that a spontaneous mutation caused your child to have CF. One spontaneous mutation would create a carrier but to create a child with CF would require two!! Highly unlikely, in fact i'd say almost impossible to create a CF child without parents of carrier status. Hope this makes sense. Doctors can't be relied upon for their biological facts hehe <img src="i/expressions/face-icon-small-smile.gif" border="0">

 

[anonymous]

above poster here...wikipedia says the delta508 mutation is probably 52 000 years old!!

<a target=_blank class=ftalternatingbarlinklarge href="http://en.wikipedia.org/wiki/Cystic_fibrosis
">http://en.wikipedia.org/wiki/Cystic_fibrosis
</a>

 

[skh]

Welcome SeanP! I don't have an answer to your question since I am pretty much gene ignorant. <img src="i/expressions/face-icon-small-smile.gif" border="0">

 

[julie]

SeanP,

I have not heard of the term "spontaneous mutation" but there are a few cases of mutations doubling from a parent during conception.

For example, say a dad carries 1 CF mutation and mom carries none. Sometime during conception, the baby ends up with 2 of Dad's chromosome 7's (chromosome 7 carries the CF muation) instead of 1 chromosome 7 from mom and 1 from dad. And it just so happens that in this case, that it is the chromosome from dad that harbors the CF mutation on it that gets passed on. So then the baby ends up with CF because he/she has 2 CF mutatons, although mom is a NOT a carrier. It is along the same lines as how someone ends up with downs, they are one chromosome short... it is definately medically possible and if I recall any of the people or stumble upon info, I'll surely post it on here for you.

Does this make sense? I use to recall the names of some people with situations like this (they are VERY rare, only a handful known in the US) but I just can't remember right now.

Also, welcome to the site!!!!!!!!!!!!

 

[anonymous]

wecome and thats not true yor docs gone made, both parents have 2b carriers, for ofspring to have cf, im very sure, can explain if you require.cj

 

[monique6]

Hi. I am 41 with CF and I have 4 kids. My triplets are 10 and my oldest daughter is 13. Anyway, my husband was tested to see if he was a carrier for CF when we wanted to have and go thru the process of having kids. We went to a genetic specialist. If both parents are not carriers, then your kids can not have CF. My kids are definitely carriers, being they received one of my genes. Could you imagine the risk if this was true of people with CF having kids? I'm not sure I would of taken it. Anyway, I just know what we went thru. My triplets were born early, but there are healthy. My oldest is healthy too. My son has hydropheliouos (water on the brain) from being born at 29 weeks. I thank God my kids are ok and that is all we pretty much had to deal with, other than some other endrocrine issues. Hope I was helpful.

 

[TCNJcystic]

Ahh I'm at a loss right now because I know I was just very surprised to hear about someone being born with CF to parents who were not carriers. The gene mutation can occur though. It's highly rare. If spontaneous gene mutations were impossible, CF would never have begun!

 

[StevenKeiles]

Well Sean,

Just about everything that everyone has said is mostly true. Yes there are spontaneous mutations. They are called de novo. These are mutations that occur in the child but were not inherited from either parent. The likelihood for that to happen to both chromosomes is very rare. However it could happen to one chromosome and I have seen it happen a couple of times. A mutation rate of 1 in 10,000 would be considered a very high new mutation rate. So as you can see it is still rare.

I believe it was Julie who described uniparental disomy which is when the same mutation is inherited twice from the same parent. Also rare but does happen.

Also it is possible for some CF carriers to have some mild CF like symptoms as you describe.

Now on to the more likely scenario which is that an affected individual carries two mutations with one inherited from each parent. Most mutations are rare so just because they do not show up on a panel does not mean they are not there. If a panel does not detect the mutations a complete sequence analysis needs to be performed.

I must add this is definitely not your average group when it come to molecular genetic knowledge. You should all pat yourselves on the back, (no pun intended)

Steven Keiles, MS
Director of Genetic Services
Ambry Genetics

 

[julie]

YES, IT IS POSSIBLE to have only one parent as a carrier and HAVE YOUR CHILD END UP WITH CF. It is EXTREMELY rare, but still does occur. Just in the same way that downs syndrome occurs (1 less chromosome). I posted about it in my comment earlier a little bit further up.

Nothing in the medical field is absolute and I'd have to disgree with those that say your doctor is mad. Maybe he/she didn't explain it to you very well, but IT IS POSSIBLE.

Monique, congrats on your tiplets.

 

[julie]

Whoooooooooooooo, Ambry genetics is onboard!!! Thanks for refreshing my memory steve, uniparental disomy.... CF is not the only "disease" that UD occurs right?

 

[SEANP]

Thanks to all of you who replied. Thanks Steven you made alot of
sense, and thanks to Yoga, I can pat myself on the back.  We
all learned that there are always exceptions to the norm.