Update on Cash

okok

New member
Hi

I found some information on the mutation R297Q. It states that it is a rare polymorphism and when paired with df508 on the opposite chromosome does NOT cause disease.
here is a link: <a target=_blank class=ftalternatingbarlinklarge href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8680407&dopt=Abstract
">http://www.ncbi.nlm.nih.gov/en...7&dopt=Abstract
</a>

i also found some info from sickkids on the other mutation r74q which sounds like it could possibly be disease causing:

<a target=_blank class=ftalternatingbarlinklarge href="http://www.genet.sickkids.on.ca/cftr/MutationDetailPage.external?sp=1082
">http://www.genet.sickkids.on.c...xternal?sp=1082
</a>

there has been one person who had chronic pancreatitis and also had this mutation and no other cf mutations. so this one could be causing trouble for your son????

Good luck with you pulmo visit. I hope it will be helpful for you and that your son will get the treatment he needs. It sounds like your son might be a good canidate for the nasal potential difference test if that is available. Without remembering your son's symptoms (other than constipation) which in the case CF really does not have a unique treatment (as opposed to other causes of constipation), I would suggest that they go ahead and treat him as if he has CF or at the very least to moniter him closely in case he develops symptoms of CF.

Again good luck and let us know how it goes.

PS... i just saw in the update on the sickkids report that the other chromosome for the person with chronic pancreatitis had your child's other mutation R279Q. so i guess that person did not have CF but did eventually develop chronic pancreatitis...? I have heard that some CF carriers are more susceptable to chronic pancreatitis but i think it is mostly a hypothesis. Anyway i am sure your doctor will much more helpful than me. Hopefully anyway!
 
M

momofcash

Guest
Thank you for the links. Speaking with the geneticist at children's she said Ambry had record of only 2 children with the R297Q and the R74Q and they both had pancreatitis. Neither of them had the other mutation. Its overwhelming.
 
M

momofcash

Guest
Thank you for the links. Speaking with the geneticist at children's she said Ambry had record of only 2 children with the R297Q and the R74Q and they both had pancreatitis. Neither of them had the other mutation. Its overwhelming.
 
M

momofcash

Guest
Thank you for the links. Speaking with the geneticist at children's she said Ambry had record of only 2 children with the R297Q and the R74Q and they both had pancreatitis. Neither of them had the other mutation. Its overwhelming.
 

StevenKeiles

New member
Just a point of clarification for everyone. These two mutations appear to be linked on the same chromosome, so they will usually appear together. We have seen them more than a few times. However, in most cases these were the only mutations identified. A couple of these patients did have pancreatitis along with a patient who did have another mutation on the other chromosome.

Regarding CF carriers being more susceptible to pancreatitis, it is more than a hypothesis. There are several published reports documenting this association including a report that we published in October in the journal Pancreas.

In addition, you need to be careful about what is listed in the mutation databases because often they are based on only one or two families so it may not be a true representation of the clinical picture. We usually have more patients in our database then what is listed in the literature so it gives us a lot more information to go on. Of course over time and gathering more information it will only become more helpful.

Steve
 

StevenKeiles

New member
Just a point of clarification for everyone. These two mutations appear to be linked on the same chromosome, so they will usually appear together. We have seen them more than a few times. However, in most cases these were the only mutations identified. A couple of these patients did have pancreatitis along with a patient who did have another mutation on the other chromosome.

Regarding CF carriers being more susceptible to pancreatitis, it is more than a hypothesis. There are several published reports documenting this association including a report that we published in October in the journal Pancreas.

In addition, you need to be careful about what is listed in the mutation databases because often they are based on only one or two families so it may not be a true representation of the clinical picture. We usually have more patients in our database then what is listed in the literature so it gives us a lot more information to go on. Of course over time and gathering more information it will only become more helpful.

Steve
 

StevenKeiles

New member
Just a point of clarification for everyone. These two mutations appear to be linked on the same chromosome, so they will usually appear together. We have seen them more than a few times. However, in most cases these were the only mutations identified. A couple of these patients did have pancreatitis along with a patient who did have another mutation on the other chromosome.

Regarding CF carriers being more susceptible to pancreatitis, it is more than a hypothesis. There are several published reports documenting this association including a report that we published in October in the journal Pancreas.

In addition, you need to be careful about what is listed in the mutation databases because often they are based on only one or two families so it may not be a true representation of the clinical picture. We usually have more patients in our database then what is listed in the literature so it gives us a lot more information to go on. Of course over time and gathering more information it will only become more helpful.

Steve
 

JazzysMom

New member
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>StevenKeiles</b></i>

Just a point of clarification for everyone. These two mutations appear to be linked on the same chromosome, so they will usually appear together. We have seen them more than a few times. However, in most cases these were the only mutations identified. A couple of these patients did have pancreatitis along with a patient who did have another mutation on the other chromosome.


Regarding CF carriers being more susceptible to pancreatitis, it is more than a hypothesis. There are several published reports documenting this association including a report that we published in October in the journal Pancreas.



In addition, you need to be careful about what is listed in the mutation databases because often they are based on only one or two families so it may not be a true representation of the clinical picture. We usually have more patients in our database then what is listed in the literature so it gives us a lot more information to go on. Of course over time and gathering more information it will only become more helpful.



Steve</end quote></div>

Steve this is such great feedback and helpful. I do appreciate that extra effort you give and being available for ??. As you know many of the newly dx are just trying to obsorb all the info and its nice to have Ambry on board here to help answer the uncertainties.
 

JazzysMom

New member
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>StevenKeiles</b></i>

Just a point of clarification for everyone. These two mutations appear to be linked on the same chromosome, so they will usually appear together. We have seen them more than a few times. However, in most cases these were the only mutations identified. A couple of these patients did have pancreatitis along with a patient who did have another mutation on the other chromosome.


Regarding CF carriers being more susceptible to pancreatitis, it is more than a hypothesis. There are several published reports documenting this association including a report that we published in October in the journal Pancreas.



In addition, you need to be careful about what is listed in the mutation databases because often they are based on only one or two families so it may not be a true representation of the clinical picture. We usually have more patients in our database then what is listed in the literature so it gives us a lot more information to go on. Of course over time and gathering more information it will only become more helpful.



Steve</end quote></div>

Steve this is such great feedback and helpful. I do appreciate that extra effort you give and being available for ??. As you know many of the newly dx are just trying to obsorb all the info and its nice to have Ambry on board here to help answer the uncertainties.
 

JazzysMom

New member
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>StevenKeiles</b></i>

Just a point of clarification for everyone. These two mutations appear to be linked on the same chromosome, so they will usually appear together. We have seen them more than a few times. However, in most cases these were the only mutations identified. A couple of these patients did have pancreatitis along with a patient who did have another mutation on the other chromosome.


Regarding CF carriers being more susceptible to pancreatitis, it is more than a hypothesis. There are several published reports documenting this association including a report that we published in October in the journal Pancreas.



In addition, you need to be careful about what is listed in the mutation databases because often they are based on only one or two families so it may not be a true representation of the clinical picture. We usually have more patients in our database then what is listed in the literature so it gives us a lot more information to go on. Of course over time and gathering more information it will only become more helpful.



Steve</end quote></div>

Steve this is such great feedback and helpful. I do appreciate that extra effort you give and being available for ??. As you know many of the newly dx are just trying to obsorb all the info and its nice to have Ambry on board here to help answer the uncertainties.
 

okok

New member
Thanks steve,

I wondered if they were linked because i think i saw abstracts for both mutations and they were both cited as occuring among people with french heritage....

Steve, are you saying that in the article (link below) where individuals were found to have DF508 and R297Q without any symptoms of disease i can also assume these individuals also have r74Q on the same chromosome? If so, this is great news for cash since his mutations are paired with g524x! If you don't know that is ok. I can get the PDF and read the whole article which might help answer the question. <a target=_blank class=ftalternatingbarlinklarge href="http://www.ncbi.nlm.nih.gov/en...7&dopt=Abstract">http://www.ncbi.nlm.nih.gov/en...7&dopt=Abstract</a>

I was just curious since I have heard of situations when having two CFTR mutations on one chromosome (can't remember the mutation names off the top of my head) can negatively affect protein function even though the mutations individually have no or little effect on the protein. It doesn't sound like this is an issue for cash though.

Also thanks so much for the info on carriers and pancreatitis too. I'm really glad you cleared that linkage info up for me. Everything makes much more sense now.
 

okok

New member
Thanks steve,

I wondered if they were linked because i think i saw abstracts for both mutations and they were both cited as occuring among people with french heritage....

Steve, are you saying that in the article (link below) where individuals were found to have DF508 and R297Q without any symptoms of disease i can also assume these individuals also have r74Q on the same chromosome? If so, this is great news for cash since his mutations are paired with g524x! If you don't know that is ok. I can get the PDF and read the whole article which might help answer the question. <a target=_blank class=ftalternatingbarlinklarge href="http://www.ncbi.nlm.nih.gov/en...7&dopt=Abstract">http://www.ncbi.nlm.nih.gov/en...7&dopt=Abstract</a>

I was just curious since I have heard of situations when having two CFTR mutations on one chromosome (can't remember the mutation names off the top of my head) can negatively affect protein function even though the mutations individually have no or little effect on the protein. It doesn't sound like this is an issue for cash though.

Also thanks so much for the info on carriers and pancreatitis too. I'm really glad you cleared that linkage info up for me. Everything makes much more sense now.
 

okok

New member
Thanks steve,

I wondered if they were linked because i think i saw abstracts for both mutations and they were both cited as occuring among people with french heritage....

Steve, are you saying that in the article (link below) where individuals were found to have DF508 and R297Q without any symptoms of disease i can also assume these individuals also have r74Q on the same chromosome? If so, this is great news for cash since his mutations are paired with g524x! If you don't know that is ok. I can get the PDF and read the whole article which might help answer the question. <a target=_blank class=ftalternatingbarlinklarge href="http://www.ncbi.nlm.nih.gov/en...7&dopt=Abstract">http://www.ncbi.nlm.nih.gov/en...7&dopt=Abstract</a>

I was just curious since I have heard of situations when having two CFTR mutations on one chromosome (can't remember the mutation names off the top of my head) can negatively affect protein function even though the mutations individually have no or little effect on the protein. It doesn't sound like this is an issue for cash though.

Also thanks so much for the info on carriers and pancreatitis too. I'm really glad you cleared that linkage info up for me. Everything makes much more sense now.
 

StevenKeiles

New member
okok,

I was not able to access the link, so I can't comment on that paper. One thing to remember is that all mutations are variable and how it affects one person is no guarentee of how it might affect others.

Some with the same mutations can have significant symptoms and other may have few if any symptoms.

You can make generalities but you can never predict exactly regarding the type of mutations that are found the effects they will have in any one person.

Hope that helps.

STeve
 

StevenKeiles

New member
okok,

I was not able to access the link, so I can't comment on that paper. One thing to remember is that all mutations are variable and how it affects one person is no guarentee of how it might affect others.

Some with the same mutations can have significant symptoms and other may have few if any symptoms.

You can make generalities but you can never predict exactly regarding the type of mutations that are found the effects they will have in any one person.

Hope that helps.

STeve
 

StevenKeiles

New member
okok,

I was not able to access the link, so I can't comment on that paper. One thing to remember is that all mutations are variable and how it affects one person is no guarentee of how it might affect others.

Some with the same mutations can have significant symptoms and other may have few if any symptoms.

You can make generalities but you can never predict exactly regarding the type of mutations that are found the effects they will have in any one person.

Hope that helps.

STeve
 

AnD

New member
Yes, thanks for the pancreatitis info <img src="i/expressions/face-icon-small-wink.gif" border="0"> . I thought I had read that somewhere, and my paternal grandmother and I took the same enzymes when I was a kid, due to her chronic pancreatitis. One of my paternal uncles has also been hospitalized with it.
 
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