Neuron offers clues to why autism spectrum disorder (ASD) is more common in boys than in girls, say researchers. They found that a single amino acid change in the "NLGN4" gene, which has been linked to autism symptoms, may drive this difference in some cases.
Researchers led by Katherine Roche from National Institutes of Health (NIH) in the US, compared two NLGN4 genes, (one on the X chromosome and one on the Y chromosome), which are important for establishing and maintaining synapses, the communication points between neurons.
Every cell in our body contains two sex chromosomes. Females have two X chromosomes; males have one X and one Y chromosome.
Until now, it was assumed that the NLGN4X and NLGN4Y genes, which encode proteins that are 97 per cent identical, functioned equally well in neurons.
But using a variety of advanced technology including biochemistry, molecular biology, and imaging tools, the study, published in the journal Neuron, discovered that the proteins encoded by these genes display different functions.
The NLGN4Y protein is less able to move to the cell surface in brain cells and is therefore unable to assemble and maintain synapses, making it difficult for neurons to send signals to one another.
When the researchers fixed the error in cells in a dish, they restored much of its correct function.
"We really need to look at NLGN4X and NLGN4Y more carefully. Mutations in NLGN4X can lead to widespread and potentially very severe effects in brain function, and the role of NLGNY is still unclear," said study first author Thien A Nguyen.
The research team found that the problems with NLGN4Y were due to a single amino acid. They also discovered that the region surrounding that amino acid in NLGN4X is sensitive to mutations in the human population.
In females, when one of the NLGN4X genes has a mutation, the other one can often compensate. However, in males, diseases can occur when there is a mutation in NLGN4X because there is no compensation from NLGN4Y, the researcher said.
"The knowledge about these proteins will help doctors treating patients with mutations in NLGN4X better understand their symptoms," said Dr Roche.