Humans are the product of many equations. The coming together of their parents, the influence of their families, the impact of their schools and peer groups and surrounding cultures, and many other influences. And, at the base of all of this, we humans are the product of two sets of 23 chromosomes that join together at conception. Our chromosomes, when joined post-conception, form diploid genomes that contain well more than 6 billion individual DNA base pairs. Contained in our genomes as humans are around 19,000-20,000 protein-coding genes distinct to us as a species. And, as for differences between us as individuals, only about .1% of each of our genomes is unique. We are remarkably similar in our makeup.
However, variations do occur, and even very minor variations can result in very significant differences. This past week, we learned of a seemingly minor variation in Mira’s genetic code that will result in some significant differences. Up until about 5 days ago, and using working diagnoses provided by multiple care providers, we had been attributing Mira’s unique physical attributes and delays to Cerebral Palsy, which is most often thought of as brain damage that occurs sometime in utero or during the birth process. We even thought we had possibly identified the potential moment when this damage occurred. However, and just to be as thorough as possible in our efforts to identify the cause of her troubles, we submitted blood samples for DNA testing.
While in utero, we had DNA testing done at a level that sort of just skimmed the surface. This testing basically just counted her chromosomes to see if she had the right number of chromosomes and to ensure that they were all intact. Nothing showed up in these tests. After she was born and when we first started noticing delays in her motor development, we submitted additional samples for a chromosomal microarray test. The microarray testing was a more in-depth look at her genome, and is a technique which allows a geneticist to determine whether particular genes are on or off, whether they are being expressed or not. This test also allows a geneticist to search for extra or missing chromosomal segments, i.e. insertions or deletions, duplications and abnormalities. This test too turned up nothing of note. At this point, we had one final test we were willing to undergo, and this test is referred to as whole exome testing.
Whole exome testing is a technique for sequencing all of the expressed genes in a genome. This is a fantastically complex and in-depth review of an individuals expressed genes that allows a geneticist to identify variants that alter protein sequences. So while previous tests were searching for insertions or deletions, this test was looking for “misspellings,” or instances where a particular nucleobase has been replaced by an incorrect one. In human DNA, there are four nucleobases, referred to by the first letter of their name – A, T, G, and C. A always pairs with T, and G always pairs with C. Geneticists have described many genes, and know which nucleobase is supposed to be in particular spots, and through exome testing, they can determine if the incorrect nucleobase may be in a particular spot.
In Mira’s case, such a misspelling exists. Misspellings occur, and in some places, a misspelling may be rather benign or ineffectual, or they may indicate than an individual may have a higher chance of developing a particular illness. In Mira’s case, the misspelling has led to more acute symptoms and may lead to even more on down the road.
In Mira’s case, the misspelling occurs in her GNAO-1 gene, in sequence 709, and we were told that there is an A where there is supposed to be a G. There is a more particular location than that, but we don’t know what it is yet. If you google GNAO-1 and start reading the limited studies available, you will start to get the sense that this is not a particularly pleasant diagnosis. Additionally, you will get a sense of how incredibly rare it is. So rare in fact, that it does not actually have a name aside from “GNAO-1 mutation.” We have heard statistics that there are less than 50 individuals worldwide who have this particular diagnosis, but we do not know for sure due to the limited availability of exome testing to economically disadvantaged individuals, or those who don’t want the testing, or those who just haven’t been tested yet. Additionally, this particular gene was only described around 5 years ago, so who knows. Maybe there are a lot of individuals with this particular diagnosis, who like us, think they are dealing with CP but in fact are dealing with something much different.
The mutation can occur in different places, as I sort of indicated. And the data available is not comprehensive enough to tell whether or not the location of the mutation leads to different outcomes or symptoms. Additionally, as far as we were told, the mutation does not occur in either of our genomes so it likely was not inherited.
As far as what we can expect in the future – we don’t know, and what we do know we are not really ready to talk about. Needless to say, we are scared. We are scared for our daughter, scared for our family, and scared of the unknown – which is an increasingly large forest we are finding ourselves in. But, we are smart, we are determined, and we are in love with our beautiful and sweet Mira with the fiercest sort of love imaginable.
I want to apologize to anyone who donated to our fund under the pretense that Mira had Cerebral Palsy. We honestly thought that was what it was based upon many conversations we have had with her care providers. But, her care needs at this point are the same. She will still need a wheelchair, a shower chair, and other adaptive equipment. Our approach will also remain the same – be the best damned parents we can be and be the parents our daughter needs us to be at all times. We will act and react accordingly as our circumstances grow and change, and we will love her with profound dedication through it all.
While we feel strongly about being open and honest regarding Mira, and regarding the GoFundMe funds that were raised, we also request a couple things from everyone reading this. First, be careful with your research. It keeps me up at night, occupies my thoughts during the day, and occupies many tabs on my internet browser. It is scary, it is gloomy, and it doesn’t change how we parent. Second, please respect our privacy at this time. We are working through something that is very difficult for us emotionally, and will talk more about it as we know more and as we feel comfortable. We want to share our story, but we want to share it on our terms. I’m sorry for this, but you can trust that we are dedicated to letting the world learn what Mira has to teach us.
I do want to report that Mira has made some wonderful progress in the past couple of months at school, with the help of her amazing therapy team and classroom teachers. We will be forever grateful for their love and dedication. I would describe these great strides, but I am going to leave that up to Nikki.
I want to tell you all how thankful we are for your support. In a world that is increasingly scary and divided, we are floored by the outpouring of generosity, prayers, good thoughts, messages, and phone calls we have received. We have a strong family, and a strong network, and we are confident that we can weather the storms as they may come. We love you all, and thanks again.
Be kind –