Emma is a unique yet important member of the CHD2 community because of the discovery of her ultra-rare genetic problem that is quite different from the typical case of CHD2.
Emma has a deletion of a long-noncoding RNA (lncRNA) called CHASERR that causes her to produce too much CHD2. She is the first person in the world diagnosed with this disorder. In fact, her doctors think she is the first person in the world with any genetic disease caused by a noncoding RNA.
Emma’s genetic journey started very shortly after birth and took almost 5 years to complete. At 5 months, she had her second brain MRI and it showed that the myelin in her brain, which is a type of wiring critical to delivering messages throughout the brain, was not forming like it should be. This led her family to proceed with whole exome sequencing and a variety of other metabolic tests. After consulting with experts around the world and running every clinical test that doctors could think of, her family was encouraged to pursue whole genome sequencing, which was only available on a research basis. Emma was enrolled in both the Rare Genomes Project at the Broad Institute and the Undiagnosed Diseases Network, a NIH funded research study from the NIH Common Fund.
In December of 2019, Emma was identified as having a deletion of the first three exons of her Chaserr gene and these were believed to be the cause of Emma’s problems. Thankfully and luckily, one of the researchers on Emma’s case discovered a preprint paper from the Weizmann Institute in Israel that discovered the Chaserr gene and was able to connect the dots. For most families, a genetic report is the end of the diagnostic journey – for Emma, this was the start of a second diagnostic journey. Emma’s diagnosis was so rare that scientists needed to validate the genetic results by studying her cells to validate that she was producing too much Chd2. Additionally, the scientists really wanted to find a second case and set on a global scavenger hunt.
After 18 months of hard work by a global team of scientists, Emma finally had a confirmed diagnosis. First, scientists at Northwestern University were able to clinically validate that Emma was producing too much Chd2 in induced pluripotent stem cells. Second, in the Summer of 2021, there was a second Chaserr case identified in France. Her scientific team is now working on submitting a research paper highlighting this important discovery.
Unfortunately, having too much Chd2 appears to be a more form of a Chd2 related disorder. Emma has spent over 250 days of her life in the hospital and will likely never be able to walk or talk. Nonetheless, she remains a happy, beautiful child and can melt your heart with her infectious smile. Spending time around Emma is a blessing that we cherish every single day.
The Chaserr gene is important to the Chd2 community because Chaserr may be a therapeutic target in order to upregulate Chd2 production. Her family is committed towards working with the Coalition to Cure Chd2 in order to drive treatments for all families impacted by Chd2.