Autism spectrum disorder (ASD) is a heterogeneous disorder with significant genotypic and phenotypic complexity, and definitive cause of autism to a genetic mutation has been revealed.

Previously identified genetic events like Fragile X, which account for a greater number of autism cases, are associated with other impairments, such as intellectual disability, more than autism, while some will have autism marked by gastrointestinal disorders, a larger head and wide set eyes.

In collaboration involving 13 institutions around the world, a study was made of 6,176 children with autism spectrum disorder. Led by scientists from the University of Washington (Seattle, WA, USA) they collected blood samples and genomic DNA was isolated. Molecular inversion probes (MIP) were performed using HiSeq-based sequencing (Illumina; San Diego, CA, USA) and analyzed. They utilized a custom 8 × 60K comparative genomic hybridization (CGH) array (Agilent, Santa Clara, CA, USA) with 150 base pair (bp) probe spacing across the gene body of a specific gene and predicted neighboring regulatory elements.

The scientists found that 15 of 6,176 children with ASD had a mutation in the gene encoding for chromodomain-helicase-DNA-binding protein 8 (CHD8) and all these cases had similar characteristics in appearance and issues with sleep disturbance and gastrointestinal problems. They identified a total of 15 independent mutations and no truncating events were identified in 8,792 controls, including 2,289 unaffected siblings. In addition to a high likelihood of an ASD diagnosis among patients bearing CHD8 mutations, characteristics enriched in this group included macrocephaly, distinct faces, and gastrointestinal complaints.

The most commonly researched genetic events associated with autism are chromosomal re-arrangements, called "copy number variations," in which a chunk of chromosome is copied or deleted, but no one rearrangement affects more than 1% of all autism cases. While these copy number events are associated with autism, they do not have a definitive link, or as they say among scientists, a “strong penetrance.”

Raphael Bernier, PhD, a professor of psychiatry and the lead author of the study said, “We finally got a clear cut case of an autism specific gene. This will be a game changer in the way scientists are studying autism. Although less than half a percent of all kids will have this kind of autism related to the CHD8 mutation, there are lots of implications from this study.” The study was published on July 3, 2014, in the journal Cell.

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