For the very first time, a variation in a gene has been linked to a subtype of autism. While other genes have been found where particular alleles (versions) show a correlation to autism, these have also been linked to other conditions, often more strongly, and not to specific autism characteristics.
The gene CHD8 has been a particular target for autism research in recent years, with the manufacturing of the associated protein shown to be disrupted in some people with Autism Spectrum Disorder (ASD), but not in healthy controls.
In their paper, Dr Raphael Bernier of the University of Washington and co-authors at twelve other institutions note, “Although various behaviorally defined subtypes have been proposed, these have not been tied to genetic etiology [causes], linked to treatment indicators, nor diagnosed consistently by expert clinicians.” DSM-5, the latest American Psychiatric Association classification of mental disorders has subsumed all previously recognized subtypes under the term ASD.
The paper adds, “More than 100 genes and genomic regions have been associated with ASD and >800 genes have been suggested to play a role in ASD.”
The authors wondered whether subtyping by genetics might prove more useful than by behavior. After examining 6176 people with ASD Bernier found 17 with potentially disruptive versions of the CHD8 gene. While clearly not a factor for many children with ASD, it is notable that in a sample of 6503 neurotypical controls, none had disrupted CHD8.
In a study of 15 of the children with CHD8 abnormalities the authors found important common features beyond the basis ASD diagnosis, including, “Pronounced brow ridges, wide set eyes...slender, tall build and large flat feet.” Moreover, 12 of the patients reported serious intestinal problems, a common, but far from universal, feature of ASD. Trouble sleeping was also unusually common.
CHD8 exists in other animals as well, and the authors showed that zebrafish with disrupted CHD8 genes have are constipated as a result of reduced production of enteric neurons.
"This will be a game changer in the way scientists are researching autism," Bernier proclaimed, leading to a “genetics-first approach” to classifying autism.
The authors also suggest that subtyping by gene may enable clinicians to detect specific types of ASD that would otherwise escape notice, providing better opportunities for treatment.
