Rowland's Mutations

     When I sat down to write this post I thought I had a well thought out narrative about Rowland's mutations and the implications for Rowland and our family. Then I read to Bryan what I wrote and I realized it was just a bunch of ramblings about genetics. This must be my way of processing because sometimes it feels like my brain is going a million miles a minute and all I can think about is this diagnosis and genetics and mutations and "how did this happen"? I've noticed this is happening less frequently as we get in the groove of our new daily routine. Slowly but surely I am also beginning to make sense of my thoughts and the reasons behind them. With that being said, I rewrote parts of my post and tried my best to explain the impact Rowland's mutations have on his and our lives. I hope it makes sense.

    In order for someone to have Cystic Fibrosis (CF),  both parents need to be carriers of a CF mutation and then both parents need to pass their CF mutation to their child. Because both Bryan and I are carriers of CF and we both passed our mutations onto Rowland, Rowland has CF. The odds of Rowland getting CF were one in four. 

    We received Rowlands' mutations back last week which made the CF diagnosis feel real to us. Since Bryan's family has a history of CF, we had an idea of what mutation Bryan could carry, but I had no idea that I was even a carrier. In fact I took a carrier screening while I was pregnant and it was negative. Rowland's newborn screening was negative for CF as well. 

    Since Rowland's diagnosis, we have learned that there are thousands of CF mutations, however my CF carrier screening only tested for the 40 most common mutations. Further, the newborn screening in California tested for 77 of the most common mutations. We have learned that Rowland has two rare mutations- 2184insA and H609R. Unfortunately neither of those screenings had either of those mutations on their panel which led to the false negatives.

    When the geneticist first shared with us Rowland's mutations, I started crying. For those of you that know me, you know I am a crier, but as those tears came down I found myself telling the geneticist that I was sad and fascinated at the same time. I am not sure I have ever felt those two conflicting emotions so intensely but they both were there in that moment. The reason the word "fascinated" came out of my mouth is because I had surprisingly heard of H609R. During the time we knew Rowland had CF but did not know his mutations, the geneticist suggested that my Ecuadorean ancestry could play a role in the mutation I carry. So as Bryan and I were attempting to enjoy our five year anniversary, we sat down for lunch at R10 Social House, had a drink, and what did I do? I googled "Cystic Fibrosis Ecuadorean mutations" and a research article came up about how H609R has only been found in Ecuadorean populations that have indigenous Andes ancestry. I kept that piece of information in my back pocket and was absolutely shocked to learn that that is actually the mutation Rowland has. My dad is Ecuadorean and according to Ancestry DNA I have indigenous Andean ancestry but I mean it's Ancestry DNA and this information was just a fun fact to share with people. It wasn't something that was tangible nor something that I considered to be part of my identity. To find out that my indigenous Andean ancestry has real world implications for myself and my son is mindblowing. 

    About 90% of people living with CF now have a modulator available that many call a miracle drug. It restores some function in the CFTR gene and will increase the life expectancy of those living with CF. Unfortunately 10% of people living with CF do not have a modulator available for them because of their mutations. Rowland is one of those 10% and the news was disappointing. The modulator that many people talk about is called Trikafta and it was approved by the FDA in 2019. Currently the modulator is approved for people ages six and up and they must have one copy of the mutation F508del. In addition, Trikafta is expensive so there are many countries that do not have access to this drug yet. 

    What I want more than anything is for Rowland to have access to a modulator when he is older (preferably sooner rather than later) because it will increase his life expectancy and help keep him healthy. There are some mutations that would probably not respond to a modulator including one of his mutations, 2184insA. However, there is reason to believe that H609R could respond to a modulator. Unfortunately there is not enough research to demonstrate the efficacy of a modulator in H609R. 

    I have heard that CF is most common in people with European ancestry. However, more recently I have learned that isn't necessarily true-- rather CF has been well studied and documented in people with European ancestry compared to other races. Rowland's mutation, H609R is considered a rare mutation, however after reading through research papers on H609R, these studies suggest that H609R is almost as common as F508del (a common mutation worldwide) in Ecuadorean populations meaning this mutation is probably not as rare as we think, just not documented nor well studied. 

    The reason why I am so concerned about H609R not being documented is because without documented cases, it is more difficult to study this mutation and therefore more difficult to study the efficacy of various modulators on H609R. If this research could be done in the future, it would be life changing for my son and others living with this mutation. 

    This is all so wild but I am just so grateful for the work the Cystic Fibrosis Foundation is doing-- and I know they are advocating for research to be done on mutations that haven't been well studied. What a journey this is going to be.