a boy's eye with puzzle pieces painted around it

Photo obtained from Flickr

Autism is a widely known term to describe a range of developmental disorders that may or may not be genetically related. It has become more recently known as autism spectrum disorder to account for the wide variety of ways it can be presented in humans. One symptom associated with up to 30% of autism spectrum disorders is developmental regression, meaning the loss of developmental abilities such as communication and ability to interact with one’s surroundings.
After stumbling upon a case of a young woman who, since the age of two and a half years old, had experienced extreme developmental regression, researchers performed whole exome sequencing on her genome. This is a technique that allows scientists to look for variants, or different forms of genes, that may cause certain diseases. In a paper published by the Oxford university Press in January of 2020, these researchers found compound heterozygous nonsense mutations in the TMPRSS9 gene. That is a mouth full, so let’s break it down! The term compound heterozygous means that there are two different versions of a gene present in the same location, and they are both recessive versions of that gene. Nonsense refers to the type of mutation meaning that the change that occurs happens in one single nucleotide, which is a basic building block of DNA; this nucleotide is changed to a different nucleotide that results in the early termination of that gene sequence. This mutation therefore causes a loss of function in the TMPRSS9 gene.

Although this correlation is quite interesting, conclusions cannot be drawn from a single patient.

Therefore, the research continued only this time it was performed in mice. After a PCR analysis, it was found that mice also express the TMPRSS9 gene, so changes to this gene in mice can be examined and applied to how it might react in humans. The scientists in this paper created a knockout mouse model, which means they generated mice that had loss of function versions of the TMPRSS9 gene. They then performed many behavioral assays which showed that these mice exhibited decreased social interest and social recognition. The results of this series of experiments lead to the indication that there is a relation between the loss of function mutants of the TMPRSS9 gene and autism spectrum disorder. The next step in this research is to try to find other human patients that have similar observable characteristics and loss of function mutations in the TMPRSS9 gene.
This theory is definitely in the very early stages of development, but this correlation has the potential to be groundbreaking in the research of autism spectrum disorders! There is still so much not known about the genetic basis of Autism. It presents in so many different ways that it could be impossible to ever determine a single gene to be the cause. But, finding even a small piece of this giant puzzle would be revolutionary!

 

Chen, C., Pal, R., Yin, J., et al (2020). Human Molecular Genetics, Volume 29, Issue 3, Pages 459–470, https://doi.org/10.1093/hmg/ddz305