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Incomudrox
06-09-2012, 07:23 AM
I got my mutation results back from John Hopkins, came back with DF508, which I knew and M1101R. I can't really find any information on it and there are no recorded instances of it in the CFR2 database, I will be the first one in the database with it? We do know it is a Class II mutation similar to DF508 but not much more than that.
So far I have figured out that my second mutation M1101R, resides on Exon 17b, it is part of the group of mutations on Cytoplasmic Loop 4 of the Cystic Fibrosis Transmembrane Conductance Regulator. It does not support biosynthesis processing. Research shows that cyclic AMP for mutation M1101R and M1101K generally have the same voltage transport ability as Wild Type CFTR. Typically they produce cor<span class="text_exposed_show">rectly synthesized proteins however the time that the chloride channel stays open is limited.
<span class="text_exposed_show">Meaning essentially that it probably belongs in class 3 with mutations like G551D, however remains grouped in the Cytoplasmic loop 4 category because of the other 15 mutations that are on exon 17b and reside within the cytoplasmic loop 4 that have poorly synthesized proteins and partially defective trafficking coupled with limited chloride channel open activity and/or no chloride channel formation at all.

kots66
06-09-2012, 05:09 PM
Have you read this? https://webcache.googleusercontent.com/search?q=cache<img src="i/expressions/face-icon-small-happy.gif" border="0">fdkyc0rqOcJ:www.genet.sickkids.on.ca/MutationDetailPage.external%3Fsp%3D472&hl=el&prmd=imvns&strip=1

Also, where did you find the rest of that information?

kots66
06-09-2012, 05:15 PM
Oh, the forum software messed up the link when I pasted it, here's a shortened link with bit.ly: http://bit.ly/KW4h1c

Incomudrox
06-10-2012, 08:42 PM
<a href="http://www.jbc.org/content/271/25/15139.full.pdf">http://www.jbc.org/content/271/25/15139.full.pdf</a> thats where I got that from.

MAC512
06-11-2012, 01:47 AM
I read that same article because my daughter's mutation was mentioned in it. Vertex has an Iphone app for mutations and M1101R was not listed but M1101K was listed as a class 2 mutation. I've had different studies classify my daughter's mutation differently. The app says class 2, but other studies have hers listed it as class 4. From some of the posts it sounds like the classifications aren't perfect as far as protein getting to the cell surface. That some DF508 (Class 2) people have had some good results with Kalydeco indicating that some protein is getting to the surface (which class 2 very little if any should be at the surface). Good luck.

Incomudrox
06-11-2012, 08:55 AM
So are you saying your daughter is M1101K? There is going to be a lot of testing needed to be done to figure out which mutations Ivacaftor will work on. However I am still not sure I would try it given the chance. I've been playing it out over and over.

MAC512
06-11-2012, 11:32 AM
No she is DF508 and R1066H

MAC512
06-11-2012, 11:41 AM
Hopefully everyone gets the chance to try it that wants to. My daughter is only 6 months old so she isn't old enough and I'm not sure at what age we would start trying them.

LittleLab4CF
06-11-2012, 09:52 PM
Incomudrox, I follow you, and others, with interest. I was a little surprised that you appear to have repeated your genetic test. Am I understanding that correctly? The reason I ask is I am considering repeating my test. Ambry toasted the first test in some new equipment in 2002 and repeated it when more blood was sent to them in 2003. It is nearly a decade since my genetic test and technology improvements now tease out considerably more CFTR gene mutations. I was diagnosed at 51 (in 2001) using first a pancreatic function test followed by a sweat test. My genetic test classifies me as a carrier; heterozygous s1235r, homozygous M470V with 7T/7T polymorphism. My CF doc is a pulmo specialist and unremarkable when it comes to lung capacity. I get a little tired of his reminding me "I am just a carrier". To be certain, I am grateful for adequate lungs, but they are far from average. Mostly I always have some lung infection going on, reducing my O2 to a level, that I should be on it at night. This is to say that my CF doc isn't clueless, prescribing night oxygen.

If this is a repeated test for you, why did you have it?
If not, how was your DF508 determined?
Were there any insurance hoops you had to jump through to repeat the test? My test ran about $3K in 2002, what does it run now?
Outside of possibly learning more, I seriously doubt it will suddenly qualify me for Kalydeco, etc. but maybe this isn't impossible?
But as a rule, I ask if anything actionable will result by having a medical test. So far the best I can see is having "SEE I TOLD YOU SOMETHING WAS WRONG WITH ME"

LittleLab4CF
06-11-2012, 10:42 PM
That is it could emblazon my tombstone one day. Ok, that one has whiskers, but there is a mixed bag with going 50 years wo/Dx. I have a team of doctors, and have had just a few GPs. With the failure of doctors including my CF clinic, malnutrition has taken its toll. I am certain the Team of Doctors at National Jewish is fantastic. I survived without my CF Dx 50 years treating my symptoms using my own team of doctors who agreed to communicate with each other and coordinate through my GP. It was imperfect, but now I have a Dx, I don't get the "you've got the worst case of whatever you have, that we have seen". Antibiotics, antiviral and analgesics come much easier.

Incomudrox
06-11-2012, 10:56 PM
@LittleLab4CF

As you follow my posts with interest, I take a lot of stock in the things you post as well. You always seem to have a good way of telling a story with the example. Something someone with great life experience as yourself can do, and do it well.

I was dx'd in 1997 (one month from my 8th birthday). I was diagnosed by sweat test. When my genetic testing was done, it was a small 23 mutation panel at that time and full sequencing was out of the question. Up until recently, with the advent of Kalydeco there has been no reason to really know as far as any doctor I have seen was concerned. Alas it was time to get it done.

1st go around (in December 11) my spit sample was sent to Ambry. However weeks went by and we heard nothing from them. So we started to inquire something got lost in translation at some point and they either botched my sample or lost it. At the same time we found this out we also learned that John Hopkins was doing the CFTR2 project.

So we filled out the paper work, and sent it off to them. 2 weeks later we got my "study identification number" and then we were able to send a blood sample. 8-10 weeks later (i have lost count now) I have my resutls. They are doing this for FREE as a research study of course I'm not sure how this would work with you as you don't already have a CF dx. But the nature of the mission of the CFTR2 project would lead me to believe they would still be interested in doing your genetic sequencing with what you do already know to find out more.

Hopefully this helps.

For the record, I will not be persueing Kalydeco for myself at this time.

LittleLab4CF
06-12-2012, 04:18 AM
Oops, you caught me. My lengthy posts are serious stuff hidden in stories. Thank you for the history of your Dx process. Also if I or insurance has to pay Johns Hopkins, I will be investigating repeating my genetic test there. I have an increasing desire to understand more fully the characteristics of my disease presentation. A different test outcome, or not, either way has personal value. Even as I write this, my mind is made up in spite of it breaking my rule of an actionable outcome.

Kalydeco is a crack in the wall. I firmly believe in most Cfers lifetime, a design specific drug family will treat all combinations of CFTR mutations ideally without side effects. My last patent automated gene harvesting from a few hundred base pairs all the way up to whole discrete cancer cells i.e. Duke's hopes of designer cancer treatment. Probably Duke's program will never recover but a lot of valuable pieces can have the ashes dusted off and already a phoenix is rising. Again, thank you.

Incomudrox
06-15-2012, 08:19 AM
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>LittleLab4CF</b></i>. Kalydeco is a crack in the wall. I firmly believe in most Cfers lifetime, a design specific drug family will treat all combinations of CFTR mutations ideally without side effects. My last patent automated gene harvesting from a few hundred base pairs all the way up to whole discrete cancer cells i.e. Duke's hopes of designer cancer treatment. Probably Duke's program will never recover but a lot of valuable pieces can have the ashes dusted off and already a phoenix is rising. Again, thank you.</end quote>

This.

Keepercjr
06-20-2012, 03:34 AM
Hi There!

I haven't had the chance to get on this site too much lately (been working a lot lately but it has slowed finally). I have those 2 mutations. And I am taking Kaly. I have not had a follow up visit with my CF team (they are 200 miles away) but I do plan to visit them soon - hopefully in the next few weeks). I have NO idea if it is helping me or not but I am leaning towards thinking it is. If I show no change (or worse yet, a decline) in my PFTs I will stop taking it. But I will continue to take it till I at least have some data. It certainly isn't a miracle cure for our mutations but I hold on to the hope that it is helping....