I discovered that a suspicion I have held for a long time about CF isn't an original thought. Imogene, our fearless Founder of CysticFibrosis.com and I were talking some time back and when I remarked that CF MUST have another gene that controls the degree of disease penetration, severity and something to do with onset or changes. She almost screamed when she said that her husband had been saying this for years.
We talk about genes turning on. A gene turns on causing breast cancer to develop or cardiac disease develops when a gene becomes active and so forth. My own journey with chronic illness generally follows the disease prevalence in the population my age. As a young child, I caught every head and chest bug that walked by our house, most kids did. I still feel sympathy for the fired teacher who misunderstood a reduction in Facebook security and told some fellow teachers that kids are little germ bags. She was quite sick from a bug or bugs from the bags of germs and missing work when she made the remark. It turned out that some of her students and several parents were following the teacher on Facebook. Oops.
Anyway, back to disease onset and our genes. We have super tiny genes, that aren't even part of the chromosome structures. Some are hidden in the cell furnaces, mitochondria, many of which can determine our ancestral origins, some are small molecule genes, found in the protoplasm of cells. We have genes that act big, like the genes in development of a fertilized egg into a living human being. A single gene causes a limb to form, called limb bud genes, in the laboratory, we can take one of the limb bud cells, move it to the abdomen, and a limb, arm or leg will develop, grow right out of the belly. It explains birth defects where people are born with hands attached to the shoulder, no arm to make it a useful end effector. An error in the timing of coordinating genes that determine growth, sex and much more.
CF is so popular in science, especially mammalian genetics, not because it's popular, but it is believed to be a single gene disease, behaving in Mendelian fashion, Dominant and Recessive genes and you get CF if you have two identical recessive CF genes. Even people new to CF know that with over a thousand known disease causing CFTR genes, that can cause CF, Mendelian genetics is out.
I seriously doubt that CF comes down to the set of CFTR gene mutations. Twin studies have established that identical CFTR genes does not mean identical disease presentation. I am certain that there are tens of thousands of people walking around genetically CF and will never know it, they have no symptoms or they are misdiagnosed as asthsma or Marfans disease, a nervous stomach or whatever, but not CF.
Another gene or genes are influencing where CF is going to cause issues, and possibly when. Late diagnosed CFers give me the best evidence. An Atlantic Ocean Life Guard, as Printer was in his youth, is a miracle? His two college degrees, multiple businesses he developed don't sound like a person with CF, except it is.
My paternal grandmother was a German Russian born in Waterloo Russia, now Belgium, in 1897. She's my CF Eve, I believe. She died at age ~48 of pancreatic/liver cancer. My father joined the Army in 1942, went through Basic training and was discharged due to "Neuro-Gastric" disorder. He battled GI disease and pneumonias from about the age of 42 until his death at 48. He was diagnosed based upon his autopsy results interpreted after my CF diagnosis. No great surprise, I had boundless energy, so much that I was suspected of the dreaded disease FFI, fatal familial insomnia. It was believed that I had just inherited a number of rather annoying, but disparate health issues like chronic sinusitis, ENT infections, and my father's GI mess.
Things started to go downhill when I hit about 47. Up until then, I was a globe trotting jet setter, spending an average of six months of each year over one pond or the other. It was a marathon lifestyle that very few people can sustain. I worked 90 hour weeks when I was home and worked even more when I was working internationally. This isn't what you expect of CF. By age 49 I had been to the top clinics in my area, the Mayo Clinic and such. I reached the point where I could work 32 hours per week, period. I wouldn't have done that except the company's future was riding on my completion of a huge automation project, one with serious consequences if it failed. By age fifty, I had sold my stock and was essentially bed bound.
If genetics isn't behind the precipitous deaths of my lineage at age 48, my own close call at a similar age, I'll eat dirt. It has been established that environment, in twin studies and other studies, has little effect, diet is a big one but I look at all CFers not diagnosed, or not even really sick at birth, to the late in life, interestingly around age 45-50, diagnosed who are very sick now but somehow pushed through life and excelled, to survive and be diagnosed late. Heck, age 4, 9, 12, 22, 30, any age beyond infancy to evade diagnosis means to me that other genes are impacting when the severity of CF is going to amp up.
Just a thought,