- Divya Krishnakumar
A recent study conducted at the National Institute of Neurological Disorders and Stroke (NINDS) in the National Institutes of Health, USA, suggests that a change in a single amino acid is responsible for the higher rate of autism spectrum disorder (ASD) in boys, as compared to girls.
The research team, led by Katherine Roche, Ph. D., a neuroscientist at NINDS, compared one NGNL4 each on the X-chromosome and the Y-chromosome. This gene is crucial for the formation and maintenance of synapses for the conduction of nerve impulses. Dr. Roche and her team found that the NLGN4X and NLGN4Y genes, while 97% identical structurally, synthesized proteins that showed different functions, in that the NLGN4Y gene is less capable of moving to the surface of brain cells, and thus has less capacity to maintain synapses, which makes signal transmission difficult.
The source of this issue was found to be a single amino acid. Another discovery made during the experiment was that the area around that amino acid in NLGN4X is highly vulnerable to mutations in humans. In patients with ASD and other intellectual disabilities, there are many mutations seen in this very region, which lead to a decrease in the function of the NLGN4X gene. This functional deficiency makes the gene hard to differentiate from the NLGN4Y gene.
According to Thien A. Nguyen, Ph.D., first author of the study and former graduate student in Dr. Roche’s lab, “Mutations in NLGN4X can lead to widespread and potentially very severe effects in brain function, and the role of NLGNY is still unclear.” Since females have two X-chromosomes, a mutation in one NLGN4X gene can be compensated for by the one on the other X-chromosome. However, since males only have one X-chromosome, and the NLGN4Y gene codes for a functionally different protein, no compensation occurs, which may lead to expression of autism-like symptoms.
This knowledge may also explain why NLGN4X-associated autism spectrum disorder is more common in males than females. Dr. Roche believes that the knowledge about these proteins will help doctors treating patients with mutations in NLGN4X better understand their symptoms.
For more, visit - https://www.nih.gov/news-events/news-releases/single-mutation-leads-big-effects-autism-related-gene
Comments