I just found out my son's mutation!

[amber682]

I already knew my son had one deltaF508 mutation, but di not know what other mutation was. Ambry found it, Q493X.

I was just wondering if anyone else on the forum has this mutation, or any info about it. Or maybe someone has a good link to finding out info about certain mutations.

I did a search of the forum and found nothing but one post from someone else that no one responded to. Searching the internet seems to be not turning up a lot of useful info. I think it may be a class 1 mutation, and deltaF508 is a class 2 right?

I had saved links in my favorites that people posted on here that were very interesting and talked a lot about different mutations and where they originate, etc. and was waiting to get his other mutation to look it up. Unfortunately this particular mutation is not included in any of these studies.

P.S. I know that there's a lot more to predicting the severity of the disease then just what muataions one has, like modifier genes and such. I'm just trying to find out a little more info about Q493X.

Thanks for reading and if you've got any info or a good link just let me know!!!

 

[amber682]

I already knew my son had one deltaF508 mutation, but di not know what other mutation was. Ambry found it, Q493X.

I was just wondering if anyone else on the forum has this mutation, or any info about it. Or maybe someone has a good link to finding out info about certain mutations.

I did a search of the forum and found nothing but one post from someone else that no one responded to. Searching the internet seems to be not turning up a lot of useful info. I think it may be a class 1 mutation, and deltaF508 is a class 2 right?

I had saved links in my favorites that people posted on here that were very interesting and talked a lot about different mutations and where they originate, etc. and was waiting to get his other mutation to look it up. Unfortunately this particular mutation is not included in any of these studies.

P.S. I know that there's a lot more to predicting the severity of the disease then just what muataions one has, like modifier genes and such. I'm just trying to find out a little more info about Q493X.

Thanks for reading and if you've got any info or a good link just let me know!!!

 

[amber682]

I already knew my son had one deltaF508 mutation, but di not know what other mutation was. Ambry found it, Q493X.

I was just wondering if anyone else on the forum has this mutation, or any info about it. Or maybe someone has a good link to finding out info about certain mutations.

I did a search of the forum and found nothing but one post from someone else that no one responded to. Searching the internet seems to be not turning up a lot of useful info. I think it may be a class 1 mutation, and deltaF508 is a class 2 right?

I had saved links in my favorites that people posted on here that were very interesting and talked a lot about different mutations and where they originate, etc. and was waiting to get his other mutation to look it up. Unfortunately this particular mutation is not included in any of these studies.

P.S. I know that there's a lot more to predicting the severity of the disease then just what muataions one has, like modifier genes and such. I'm just trying to find out a little more info about Q493X.

Thanks for reading and if you've got any info or a good link just let me know!!!

 

[Anns]

Hi Amber,
I don't know anything about the mutation, but I have talked to Ambrey on the phone, and they put a genetic counselor on the phone who told me about my son's mutation, how many people they have tested w/ it and their symptoms. I also posted a couple of weeks ago about an addittional test Ambry does that looks at modifiers that have some corolation to severity of lungs, i am going to ask my doc to sign off on the papers to get this done at next clinic visit, they sent the kit to my house to have it filled out by dr and sent in
Lori

 

[Anns]

Hi Amber,
I don't know anything about the mutation, but I have talked to Ambrey on the phone, and they put a genetic counselor on the phone who told me about my son's mutation, how many people they have tested w/ it and their symptoms. I also posted a couple of weeks ago about an addittional test Ambry does that looks at modifiers that have some corolation to severity of lungs, i am going to ask my doc to sign off on the papers to get this done at next clinic visit, they sent the kit to my house to have it filled out by dr and sent in
Lori

 

[Anns]

Hi Amber,
I don't know anything about the mutation, but I have talked to Ambrey on the phone, and they put a genetic counselor on the phone who told me about my son's mutation, how many people they have tested w/ it and their symptoms. I also posted a couple of weeks ago about an addittional test Ambry does that looks at modifiers that have some corolation to severity of lungs, i am going to ask my doc to sign off on the papers to get this done at next clinic visit, they sent the kit to my house to have it filled out by dr and sent in
Lori

 

[Imogene]

I did have a great conversation with Steve from Ambry..at the CF convention last Friday.
He may have some ideas..he is a genetic counselor who is available right here at our site!

Jeanne

 

[Imogene]

I did have a great conversation with Steve from Ambry..at the CF convention last Friday.
He may have some ideas..he is a genetic counselor who is available right here at our site!

Jeanne

 

[Imogene]

I did have a great conversation with Steve from Ambry..at the CF convention last Friday.
He may have some ideas..he is a genetic counselor who is available right here at our site!

Jeanne

 

[CFHockeyMom]

Here's some generic info about that "type" of mutation...

It is a nonsense mutation (ends in x) which means it result in the absence of functional CFTR (Class I).

Here's some info I copied from another post about the various classes...

<div class="FTQUOTE"><begin quote>Class I mutations lead to defects in the synthesis of stable CFTR mRNA transcripts resulting in absence of the CFTR protein. About half of all mutations in CFTR (encompassing premature termination, exon skipping, aberrant mRNA splicing, and frameshifts) are thought to fall into this class and result in complete loss of CFTR protein/function.

Class II mutations, including F508, complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive (7).

Class III mutations disrupt activation and regulation of CFTR at the plasma membrane. Thus biosynthesis, trafficking, and processing are undisturbed, but the channel may be defective with respect to ATP binding and hydrolysis, or phosphorylation. Mutations, such as G551D, tend to be associated with a severe phenotype.

Class IV mutations affect chloride conductance or channel gating and thus result in reduced chloride current. As might be expected, mutations in this class, such as R117H or P574H, are thought to confer a milder phenotype.

Class V mutations reduce the level of normal CFTR protein by alterations in the promoter or by altering splicing. Currently it is thought that a reduction in mRNA to less than 10% of normal results in disease in CF. Examples of Class V mutations include 3849 + 10kb CT, A455E, and 5T.</end quote></div>

Here's some info that Allie posted about how different classes "interact"...

<div class="FTQUOTE"><begin quote>Now, I know this is just one article, but I found it really interesting, in france, they did research of CFers with class I /I or class II/I combinations. They found a much higher likelihood of severe pancreatic disease (which we knew), but the interestig thing was they found that people with a class one mutation were more likely to be colonized with pseudo. Interesting.

<a target=_blank class=ftalternatingbarlinklarge href="http://www.pslgroup.com/dg/214BBE.htm">http://www.pslgroup.com/dg/214BBE.htm</a>

Edited to add: I lied, there's more, this is the one I was looking for in my pile earlier. In Thorax, July of 2005, there was an article about genotype and pulmonary outcome. Here's what I found :


Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival .</end quote></div>

Hope this helps.

 

[CFHockeyMom]

Here's some generic info about that "type" of mutation...

It is a nonsense mutation (ends in x) which means it result in the absence of functional CFTR (Class I).

Here's some info I copied from another post about the various classes...

<div class="FTQUOTE"><begin quote>Class I mutations lead to defects in the synthesis of stable CFTR mRNA transcripts resulting in absence of the CFTR protein. About half of all mutations in CFTR (encompassing premature termination, exon skipping, aberrant mRNA splicing, and frameshifts) are thought to fall into this class and result in complete loss of CFTR protein/function.

Class II mutations, including F508, complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive (7).

Class III mutations disrupt activation and regulation of CFTR at the plasma membrane. Thus biosynthesis, trafficking, and processing are undisturbed, but the channel may be defective with respect to ATP binding and hydrolysis, or phosphorylation. Mutations, such as G551D, tend to be associated with a severe phenotype.

Class IV mutations affect chloride conductance or channel gating and thus result in reduced chloride current. As might be expected, mutations in this class, such as R117H or P574H, are thought to confer a milder phenotype.

Class V mutations reduce the level of normal CFTR protein by alterations in the promoter or by altering splicing. Currently it is thought that a reduction in mRNA to less than 10% of normal results in disease in CF. Examples of Class V mutations include 3849 + 10kb CT, A455E, and 5T.</end quote></div>

Here's some info that Allie posted about how different classes "interact"...

<div class="FTQUOTE"><begin quote>Now, I know this is just one article, but I found it really interesting, in france, they did research of CFers with class I /I or class II/I combinations. They found a much higher likelihood of severe pancreatic disease (which we knew), but the interestig thing was they found that people with a class one mutation were more likely to be colonized with pseudo. Interesting.

<a target=_blank class=ftalternatingbarlinklarge href="http://www.pslgroup.com/dg/214BBE.htm">http://www.pslgroup.com/dg/214BBE.htm</a>

Edited to add: I lied, there's more, this is the one I was looking for in my pile earlier. In Thorax, July of 2005, there was an article about genotype and pulmonary outcome. Here's what I found :


Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival .</end quote></div>

Hope this helps.

 

[CFHockeyMom]

Here's some generic info about that "type" of mutation...

It is a nonsense mutation (ends in x) which means it result in the absence of functional CFTR (Class I).

Here's some info I copied from another post about the various classes...

<div class="FTQUOTE"><begin quote>Class I mutations lead to defects in the synthesis of stable CFTR mRNA transcripts resulting in absence of the CFTR protein. About half of all mutations in CFTR (encompassing premature termination, exon skipping, aberrant mRNA splicing, and frameshifts) are thought to fall into this class and result in complete loss of CFTR protein/function.

Class II mutations, including F508, complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive (7).

Class III mutations disrupt activation and regulation of CFTR at the plasma membrane. Thus biosynthesis, trafficking, and processing are undisturbed, but the channel may be defective with respect to ATP binding and hydrolysis, or phosphorylation. Mutations, such as G551D, tend to be associated with a severe phenotype.

Class IV mutations affect chloride conductance or channel gating and thus result in reduced chloride current. As might be expected, mutations in this class, such as R117H or P574H, are thought to confer a milder phenotype.

Class V mutations reduce the level of normal CFTR protein by alterations in the promoter or by altering splicing. Currently it is thought that a reduction in mRNA to less than 10% of normal results in disease in CF. Examples of Class V mutations include 3849 + 10kb CT, A455E, and 5T.</end quote></div>

Here's some info that Allie posted about how different classes "interact"...

<div class="FTQUOTE"><begin quote>Now, I know this is just one article, but I found it really interesting, in france, they did research of CFers with class I /I or class II/I combinations. They found a much higher likelihood of severe pancreatic disease (which we knew), but the interestig thing was they found that people with a class one mutation were more likely to be colonized with pseudo. Interesting.

<a target=_blank class=ftalternatingbarlinklarge href="http://www.pslgroup.com/dg/214BBE.htm">http://www.pslgroup.com/dg/214BBE.htm</a>

Edited to add: I lied, there's more, this is the one I was looking for in my pile earlier. In Thorax, July of 2005, there was an article about genotype and pulmonary outcome. Here's what I found :


Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival .</end quote></div>

Hope this helps.

 

[amber682]

Thanks everyone!!!

Imogene- I did think of writing a post to Steve the Ambry guy but wasn't sure if he could help with info on a certain mutation. I thought he dealt mostly with info about the genetic testing itself. I'll write him a quick post in the Ambry thread.

CFHockeyMom- I remember reading that post from Allie now that I see it, and thanks for re-posting the class info!

Anns- I read that when you originally posted it, very interesting! I think I'll look into it.

Thanks guys! I've been looking around on the internet off and on all day just trying to figure out the class (thanks Claudette!) and how common it is. The original report from Ambry found only the deltaF508 mutation but a second report was sent about a month and a half later stating that the second mutation was located and that it was also a deleterious mutation and that it is considered a severe allele associated with pancreatic insufficiency. (We already knew he had CF and was PI at the time)

 

[amber682]

Thanks everyone!!!

Imogene- I did think of writing a post to Steve the Ambry guy but wasn't sure if he could help with info on a certain mutation. I thought he dealt mostly with info about the genetic testing itself. I'll write him a quick post in the Ambry thread.

CFHockeyMom- I remember reading that post from Allie now that I see it, and thanks for re-posting the class info!

Anns- I read that when you originally posted it, very interesting! I think I'll look into it.

Thanks guys! I've been looking around on the internet off and on all day just trying to figure out the class (thanks Claudette!) and how common it is. The original report from Ambry found only the deltaF508 mutation but a second report was sent about a month and a half later stating that the second mutation was located and that it was also a deleterious mutation and that it is considered a severe allele associated with pancreatic insufficiency. (We already knew he had CF and was PI at the time)

 

[amber682]

Thanks everyone!!!

Imogene- I did think of writing a post to Steve the Ambry guy but wasn't sure if he could help with info on a certain mutation. I thought he dealt mostly with info about the genetic testing itself. I'll write him a quick post in the Ambry thread.

CFHockeyMom- I remember reading that post from Allie now that I see it, and thanks for re-posting the class info!

Anns- I read that when you originally posted it, very interesting! I think I'll look into it.

Thanks guys! I've been looking around on the internet off and on all day just trying to figure out the class (thanks Claudette!) and how common it is. The original report from Ambry found only the deltaF508 mutation but a second report was sent about a month and a half later stating that the second mutation was located and that it was also a deleterious mutation and that it is considered a severe allele associated with pancreatic insufficiency. (We already knew he had CF and was PI at the time)

 

[hikingmomde]

hi amber. i just found out that my daughter (17 mos) has the f508 and a nonsense mutation (r1158x). she must've gotten the latter from me as my pregnancy screening was negative for cf (but this mutation is only picked up on the extended panel). at any rate, she was just diagnosed about a month ago, so all of this is still new and overwhelming to us. just thought i'd share . . .

 

[hikingmomde]

hi amber. i just found out that my daughter (17 mos) has the f508 and a nonsense mutation (r1158x). she must've gotten the latter from me as my pregnancy screening was negative for cf (but this mutation is only picked up on the extended panel). at any rate, she was just diagnosed about a month ago, so all of this is still new and overwhelming to us. just thought i'd share . . .

 

[hikingmomde]

hi amber. i just found out that my daughter (17 mos) has the f508 and a nonsense mutation (r1158x). she must've gotten the latter from me as my pregnancy screening was negative for cf (but this mutation is only picked up on the extended panel). at any rate, she was just diagnosed about a month ago, so all of this is still new and overwhelming to us. just thought i'd share . . .

 

[folione]

I know it's hard to resist the desire to know how it's going to turn out down the road, but I think past experience of older CF patients and lab studies of them are not really that useful unless hearing that it's a "severe" mutation is going to make you behave differently about treatments, etc. than hearing it's a "mild" mutation.

My son's has a class 1 and class 2 mutation (dF508 and q220x) which says he's in the "severe" group - and really, all it does is make me fret about the distant future despite his being health as a horse right now. He needs enzymes, but not a very high dose, and his lungs have shown almost no tendency to get mucosy. He's cultured PsA a couple times and killed it in pretty short order and when he gets a cold it lasts no longer than and maybe even shorter than his non-CF cohorts. So what am I supposed to do with the so-called "information" about his mutations besides worry about it?

 

[folione]

I know it's hard to resist the desire to know how it's going to turn out down the road, but I think past experience of older CF patients and lab studies of them are not really that useful unless hearing that it's a "severe" mutation is going to make you behave differently about treatments, etc. than hearing it's a "mild" mutation.

My son's has a class 1 and class 2 mutation (dF508 and q220x) which says he's in the "severe" group - and really, all it does is make me fret about the distant future despite his being health as a horse right now. He needs enzymes, but not a very high dose, and his lungs have shown almost no tendency to get mucosy. He's cultured PsA a couple times and killed it in pretty short order and when he gets a cold it lasts no longer than and maybe even shorter than his non-CF cohorts. So what am I supposed to do with the so-called "information" about his mutations besides worry about it?