Hi All, I wanted to add to this thread in case my information is helpful to others as I have just learned that I am also a carrier of c.1584G>A [1716G/A] CFTR Variation (p.Glu528Glu). I also have the mild CFTR mutation 11TG-5T, which I believe is also referred to as IVS8-5T. From my brief study even when 11TG-5T is paired with a known significant pathogenic mutation, still results in asymptomatic or very mild CF. Somewhat affirming that, I can state that I am 35 y/o male and have no symptoms of CF, nor had any idea that I was a carrier of either mutation despite being screened negatively for 97 other mutations during my wife's first pregnancy, which also proves I have no fertility issues!
My wife is a carrier of the DeltaF508 mutation; she has had no further screening but based on her health and history, we assume she has no other mutations.
We now have 2 healthy children, though one is at a minimum a carrier of DeltaF508 mutation... She is now 3 and healthy. At 3 mos, she was sweat tested, which was negative as well. As a stretch potential symptom, she does suffer from mild chronic constipation but has no respiratory issues whatsoever. Our other daughter is 18 months old and also healthy, no symptoms, and she did not test positively for deltaf508 at birth during her preliminary screenings. She has not been sweat tested.
The reason I performed additional testing recently is due to my sister and brother-in-law's daughter unexpectedly being diagnosed with CF despite no family history on either side. Both parents were screened before birth and we learned that my sister was also a carrier of DeltaF508, but like me, my brother-in-law tested negatively for his panel of 97 mutations. Unfortunately, they were not so lucky as us and their daughter was born with meconium ileus and shortly thereafter diagnosed with CF after successful surgery via sweat test and a genetic workup. My brother-in-law was later found to carry a rarer gene deletion common in eastern Europe.
Almost immediately following this, my wife and I learned we were again (unexpectedly) pregnant, so my doctor had a full genetic screening performed on my CFTR gene to ensure that my original testing was accurate and that my daughter did not receive the DeltaF508 gene from me now that we knew my sister and family was linked to the common mutation. The goal was to ensure we didn't just get lucky with our first two children. My wife miscarried at 9 weeks, but the revelation that I had two potential mutations is still worrisome for us as our oldest daughter likely inherited c.1584G>A or the 11TG-5T mutation from me, unless we got lucky and my mutations are resident to a complex allele, meaning there's a chance one of my genes is actually clean and both of my mutations reside on a single allele.
My parents have had no genetic testing performed, but my mother suffers from chronic cough and significant finger clubbing, which has been diagnosed as CREST Syndrome, a rare autoimmune disease. It is my theory that this diagnosis is not correct and she is instead suffering from mild-adult onset CF, though I have no way to prove this and the more likely scenario is that I have watched to many episodes of Dr. House and am substituting Google.com for a medical degree. That said, she exhibits none of the most common expected symptoms of CREST syndrome, and we have 3 known CFTR mutations in our direct family tree, so it seems at least plausible, right?
Anyway, I will follow-up here on this thread as any new family history info or knowledge presents in relation to c.1584G>A.
My concern is that my mother's gene paring is c.1584G>A or 11TG-5T and DeltaF508 and provides a glimpse into the possible future of my oldest daughter or if future potential children were to be paired with this combo. While my mother had a healthy initial 45 years, the last 15 have been progressively worse yoy.
Best to you all,
Chase