Being diagnosed at 52 has had the unintended consequence of not being overly impressed by medical diagnosis and to a lesser extent doctors in general. When it comes to a CF diagnosis, often the spectre of most medical doctors delving into the science of genetics strikes me like a mother watching their young child lighting and throwing firecrackers.
I would hate to think that insurance companies decided to take some of my pre-Kalydeco remarks about the merits of genetic testing for CF and try to make them policy. Just kidding, I hope. I'm an old geneticist who is reasonably current in the science. Before genetic drugs that can arrest the disease in one mutation set and the completion of finding and listing all CFTR gene mutations, I saw genetic testing as little more than a novelty. It was all too often fodder for causing doubt in both the doctor and patients when there simply wasn’t enough information. Its merit was questionable, but no more. It is also just a waste to perform incrementally more inclusive genetic tests. Anything less than a full genetic assay for the CFTR gene is like a dermatologist checking your right leg for any suspicious moles when your entire skin surface is suspect. Eventually all four limbs, the head and trunk are checked but what is the logic?
My low opinion of the testing was further fueled by the interpretation of the results. Kristen was given a 5% chance of her coming up with two rare genes. If you undergo a medical test with a 5% chance of serious complications or death, you have to sign your life away. Chances are relative. With genetic testing you confirm that you have CF or you have PCD only, or possibly both, why not? A misdiagnosis here means that you may be undiagnosed for CF, something that includes the GI tract and possibly years of malnutrition caused by complications of CF. I'm paying for the 52 years doctors missed my CF, mild by definition, but time has not been kind. Malnutrition kills like slow poison and to see a 20 year old CFer with arthritis is infuriating let alone a 30 year old as I was when they discovered I had osteopenia.
The traditional definition of CF is having two identical CFTR mutations known to cause the disease. Anything else was NOT CF. This held for about 16 discoveries of additional mutations. At 2700+ mutations and thousands of "symptomatic carriers" treated as full blown CF patients, the genetic definition became a moving target. Doctors floundered when the gene of a mammal was stuffed into the lucky box of Mendel's pea seed experiments that held dominant and recessive genes with the status of black and white. Dominant genes always won completely and a pair of recessive genes were necessary for the disease or recessive genetic characteristic to present itself. Mendel was amazingly lucky to choose the particular pea plants to study because in nature, black and white seem to mix it up more often than anybody first suspected.
Genetics became tangible for the general public with the blockbuster movie "Jurassic Park". Medical doctors should have taken their kids to this movie. Although the chaos mathematician wasn't credible, in my opinion, his message was. Any time a rule is made in human genetics, count on it being partially or more likely totally wrong. More to the point we now know that a T polymorphism can act like a genuine mutation. This is about as far away from the traditional belief that you must have two identical mutations.
The topic post “Welcome Ambry Genetics” is full of genetic wisdom. It is also policy that a topic post or the threads by anybody can be withdrawn and I believe Ambry may have just been doing some house cleaning, because it’s only in archives.
I have copied a portion of this conversation. An Ambry geneticist made this offer after my rather lengthy summary of how CF and its genetics has changed as new information has been made available.
“Steve” from Ambry had this to say:
Thanks LL for a good background and update for many. Just to clarify about the 5T polymorphism issue. Everyone carries a certain number of T's that are strung together in intron 8 of the CFTR gene. Most people carry 7 or 9, and about 7% of the population carry 5. Right next to this poly T tract is another string of TG's which usually number 10 or 11, and in some cases 12 or 13. When you have 7 or 9 T's the TG number is irrelevant. However, when you have 5T's and it is paired with a higher number of TG's like 12 or 13 this actually acts like another CF mutation. The higher the TG count the more severe the mutation. So if you have a 5T with only 11 is very mild or even asymptomatic. However with 12 or 13 it is more like a moderate CF mutation and when paired with another CF mutation on the other chromosome can actually cause CF. Every body is different and there is variability with all mutation combinations so you can never predict exactly how the disease will be based on the CF mutations.
Steve - See more at:
http://forum.cysticfibrosis.com/thr...highlight=Ambry+Genetics#sthash.V561mzGd.dpuf
If you want to slog through my background and update on CF this is the link to the post just prior to Steve’s
http://forum.cysticfibrosis.com/thr...highlight=Ambry+Genetics#sthash.V561mzGd.dpuf.
I hope this helps you figure out whether or how to pursue your answers,
LL
