CHASERR

CHASERR is a long non-coding RNA (lncRNA) located upstream of the CHD2 gene. Unlike protein-coding genes, CHASERR does not produce a protein. However, it plays a critical regulatory role in controlling the expression of CHD2. Disruption or deletion of CHASERR is associated with a severe neurodevelopmental disorder.

Biological Function

CHASERR is a long non-coding RNA upstream of the CHD2 gene. While CHASERR does not make any protein, deletion of CHASERR causes its neighboring gene CHD2 to be overexpressed, leading to excess CHD2 protein levels. This dysregulation contributes to abnormal brain development.

Mutations

Deletion of one copy of the CHASERR gene has been identified as the genetic cause of the associated disorder. This loss of function leads to overexpression of CHD2 and resulting neurological symptoms.

Symptoms

Individuals with CHASERR deletion have been reported to experience:

Inability to talk
Inability to walk
Severe hypotonia (loss of muscle tone)
Global developmental delay
Intellectual disability
Facial dysmorphisms

Research at Northwestern

Neurodevelopmental disorder caused by deletion of CHASERR, a lncRNA gene
N Engl J Med. 2024 Oct 24
Ganesh VS, Riquin K, Chatron N, et al.

“Little‑Studied RNA Might Be Key to Regulating Genetic Disorders…” — This research was featured in Nature’s C&EN and covered by Northwestern’s research news.
Ulitsky I, et al.

Novel syndromic neurodevelopmental disorder caused by de novo CHASERR deletion.
NEJM. 2024.
Ganesh VS, Riquin K, et al.

Important publications from other laboratories

Rom A, Melamed L, Gil N, et al.
Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability. Nature Communications. 2019;10:5092.

Genetic Testing

Detection of CHASERR deletions can be achieved through whole genome sequencing, as protein-coding and exon-only tests may miss the region.