Researchers from the National Institutes of Health (NIH) have identified how a change in a single amino acid may be linked to symptoms of autism. In particular, they noted that this variation may explain why autism is more common in boys than girls.
For their study, the researchers compared two NLGN4 genes, responsible for creating and maintaining synapses- the communicatory points between neurons. While NLGN4X is present in the female X chromosome, NLGN4Y is present in the male Y chromosome. While females have two X chromosomes and males have one X and one Y chromosome, up until now, it has been thought that both NLGN4 types encode proteins that are 97% identical and function equally well.
However, upon examining the genes more closely, the researchers found that the proteins encoded by these genes operate differently. In particular, they noticed that the proteins encoded by NLGN4Y are less able to move to the cell surface in cells located in the brain, and are thus unable to construct and maintain synapses. This makes it difficult for neurons to communicate.
Closely inspecting the NLGN4Y gene, the researchers found that its deficits came from a single amino acid. They also found that the region surrounding NLGN4X is sensitive to mutations that may make it behave similarly to NLGN4Y. This means that, if NLGN4X genes in females undergo a mutation that hampers their ability to encode for proteins, its deficit is likely to be compensated by the function of the other, functioning NLGN4X gene. However, in males, should their NLGN4X gene be mutated to the point of producing faulty proteins, its function cannot be supplemented by NLGN4Y.
For the researchers, this means that, should mutations occur in the areas of NLGN4X that affect its ability to synthesize proteins, autism-related symptoms including intellectual deficits may occur. The researchers thus concluded that in this case, the inability of a fully-operational NLGN4X gene to compensate a diabled NLGN4Y gene may explain why males tend to be at a higher risk of developing autism than females.
A previously unknown phenomenon, Thien A. Nhuyen, the lead author of the study, said, “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.”