Researchers at the Seattle Children’s Hospital in Washington have identified variants in the ZNF292 gene that could contribute to the development of autism. Published in Genetics in Medicine, this study built upon previous work that linked the ZNF292 gene to intellectual disability, and has now identified multiple variations in the gene that could be responsible.

The ZNF292 gene encodes a highly conserved zinc finger protein that acts as a transcription factor. It influences the expression of other genes and is highly expressed in the developing human brain, supporting its critical role in neurodevelopment. It’s mainly expressed in the cerebellum, the area that contributes to cognition and controls voluntary movement. However, the exact function of this protein in neurodevelopment is unknown.

The team used a cohort of 28 families with intellectual disability and identified pathogenic ZNF292 variants via exome sequencing. The participants of the study came from six countries and were between 10 months and 24 years old. All but one had an intellectual disability. 17 of them had suspected or confirmed autism, and 9 were suspected or confirmed to have attention deficit hyperactivity disorder (ADHD). All but two had speech delays, and four had language regression or were minimally verbal.

The study identified 28 people with mutations in ZNF292. A total of 24 different mutations were found in the gene, 23 of which were spontaneous and not inherited from a parent. One family had a dominantly inherited variation that was passed down.

Magnetic resonance imaging scans from the participants showed that nine had brain abnormalities such as atypically shaped regions, and of these nine, three appeared to have blood-vessel injuries in the brain.

A broad spectrum of physical traits was also noted in the participants. 11 of them showed growth abnormalities such as short stature; 10 had low muscle tone; and three had stuff or mixed muscle tone. Nearly half the participants showed unusual facial characteristics, such as the eyes being unusually far apart or an undersized jaw, and vision problems which affected nine people in the group.

The team plan to study more individuals with variants in ZNF292 to fully understand the link between this gene’s function and the effect it has on the brain and development.