August 2026

NEUROSCIENCES

NONCODING DNA REGIONS DRIVE DEVELOPMENT OF NEURODEVELOPMENTAL DISORDERS

Featuring: Gemma Carvill, PhD

​A new study, published in Nature Communications, from the laboratory of Gemma Carvill, PhD, has uncovered variants in noncoding regulatory regions of the genome that contribute to the development of neurodevelopmental disorders.

While patients are often prescribed multiple antiseizure medications and neuropsychiatric therapies to help treat symptoms, they are not always effective and fail to target the root cause of the disorder, according to Dr. Carvill.

Nearly 17% of all neurodevelopmental disorders are caused by pathogenic structural variants that disrupt coding regions. In the study, Dr. Carvill’s team aimed to determine how structural variants in one noncoding region of the genome may drive pathogenesis in individuals with neurodevelopmental disorders.

First, the scientists used the DECIPHER (DatabasE of GenomiC VarIation and Phenotype in Humans using Ensembl Resources) database to identify 14q12 microdeletions downstream of the neurodevelopmental disorder-related gene, FOXG1, in individuals with epilepsy and related neurodevelopmental disorders.

“We thought perhaps there are some regulatory elements in this region that, if deleted, would reduce the amount of FOXG1 in much of the same way a coding variant would,” Dr. Carvill says.

Using CRISPR-Cas9 gene editing, the scientists then created 14q12 microdeletions in HAP1 human cell lines with FOXG1 expression. These deletions decreased FOXG1 protein, which is also observed in neurodevelopmental disorder patients with FOXG1 coding variants.

Next, the scientists used a chromatin conformation capture technique to identify the mechanisms driving reduced FOXG1. In regions with 14q12 microdeletions, they discovered several cis-regulatory elements promoting FOXG1 expression.

The findings demonstrate how noncoding regions of the genome can cause neurodevelopmental disorders, Dr. Carvill says, and should prompt further investigation into the effects of structural variants in other noncoding regions across the genome, which can help inform new gene-targeting therapies for patients.

“The locus is actually very challenging, and what I mean by that is we deleted a small segment, but it turns out that this whole region actually contains a lot of different cis-regulatory elements that probably act at different times in neurodevelopment, probably to switch the gene downstream on in different cell types and different times in development, and so we’re interested in doing a deep mechanistic dissection of this entire region. We can use this information to precisely target these cis-regulatory elements and restore FOXG1 expression in individuals with this condition,” Dr. Carvill says.

Aishwarya Ramamurthy, PhD, a former student in the Driskill Graduate Program in Life Sciences (DGP), was lead author of the study.

Co-authors of the study include Esther Yoon and Nicholas Bodkin, MSTP students; and Jeffrey Calhoun, PhD, research assistant professor in the Ken and Ruth Davee Department of Neurology’s Division of Epilepsy and Clinical Neurophysiology.
This work was supported by the Chicago Biomedical Consortium Catalyst Award and the American Epilepsy Society Predoctoral Fellowship.

​This article was originally published in the Feinberg School of Medicine News Center on August 6, 2026. 
Gemma Carvill, PhD, associate professor in the Ken and Ruth Davee Department of Neurology’s Division of Epilepsy and Clinical Neurophysiology, was senior author of the study published in Nature Communications.

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