A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Summer, 2018 | Number 3, Volume 32

Gene linked to subtype of autism affects cells that insulate axons in the CNS

A gene linked to a subset of autism spectrum disorders (ASD) plays a key role in the development of cells that form protective insulation around nerves in the central nervous system, a new study reveals. 

Mutations of the CHD8 gene affect a small minority of individuals with autism, causing ASD symptoms, abnormalities in the brain’s white matter, and significant gastrointestinal disturbances (primarily constipation). Individuals with CHD8 mutations typically have unusual features, including a large head circumference, a prominent forehead, and wide-set eyes. 

Chuntao Zhao and colleagues studied the role of the CHD8 gene using mice genetically engineered to not express the CHD8 protein in oligodendrocytes, which are cells that provide support and insulation to axons in the central nervous system (CNS). The researchers found that loss or mutation of CHD8 reduces the function of histone methyltransferase, which helps to activate genes needed for oligodendrocytes to develop. Using an experimental compound that inhibits a different molecule linked to CHD8, the researchers were able to “rescue” the development of oligodendrocytes, reversing white matter defects in the mice and reducing their neurological problems. 

Senior study coauthor Q. Richard Lu comments, “So far, no treatment is available for autism patients with mutations in CHD8, one of the highest risk-susceptibility genes for autism. Current studies are still at a very early stage in terms of therapeutic agents, but our findings present a potential strategy to restore the function of faulty CHD8-dependent processes.”


“Dual requirement of CHD8 for chromatin landscape establishment and histone methyltransferase recruitment to promote CNS myelination and repair,” Chuntao Zhao, Chen Dong, Magali Frah, Yaqi Deng, Corentine Marie, Feng Zhang, Lingli Xu, Zhixing Ma, Xinran Dong, Yifeng Lin, Scott Koenig, Brahim Nait-Oumesmar, Donna M. Martin, Laiman N. Wu, Mei Xin, Wenhao Zhou, Carlos Parras, and Q. Richard Lu, Developmental Cell, Vol. 45, No. 6, pp. 753-68, June 2018. Address: Chuntao Zhao, Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai 201102, China,  [email protected]


 “Scientists learn more about how gene linked to autism affects brain; study suggests modulating CHD8 might help some people with complex condition,” news release, Cincinnati Children’s Hospital Medical Center, June 18, 2018.