Kathleen Hagerty Provost | Northwestern University
Researchers from Northwestern Medicine and the Broad Institute of MIT and Harvard have identified a long non-coding RNA, CHASERR, which plays a crucial role in regulating protein production by the CHD2 gene. The absence of this RNA can lead to an overproduction of CHD2 protein, resulting in severe neurodevelopmental disorders such as autism and epilepsy.
The study, published on October 23 in the New England Journal of Medicine, highlights the significance of non-coding regions within the human genome. "There are thousands of long non-coding RNAs, but, until this study, we didn’t know what they did," said Gemma Carvill, corresponding author and assistant professor at Northwestern University Feinberg School of Medicine.
This research builds on previous findings that linked CHASERR deletion to excessive CHD2 protein production in mice. Co-senior author Anne O'Donnell-Luria noted that with just three patients studied, they were able to classify this as a new disorder. She emphasized that more long non-coding RNAs could underlie other rare genetic disorders.
Emma Broadbent was one of the first patients identified with this condition. Her father Brian Broadbent expressed hope for future treatments stemming from these findings: "We intuitively understood that this was a lot bigger than just Emma."
The implications for treatment are significant. Current therapies focus on managing symptoms rather than addressing genetic causes. Carvill's team aims to develop gene-targeting therapies using their understanding of how non-coding regions like CHASERR control gene expression.
Funding for the study came from various institutions including the National Institutes of Health and Chan Zuckerberg Initiative Donor-Advised Fund.