A multi-institutional study involving Massachusetts General Hospital (MGH) researchers has identified a chromosomal abnormality that appears to increase susceptibility to autism.
In a New England Journal of Medicine report that is receiving early online release, the investigators – most of whom are associated with the Boston-based Autism Consortium – report that a segment of chromosome 16 is either missing or duplicated in about 1 percent of individuals with autism or related disorders, a frequency that is comparable to other genetic syndromes associated with the disorder.
“While epidemiologic studies indicate a very large genetic component to autism, little is known about how specific genes are involved,” says Mark Daly, PhD, of MGH Center for Human Genetic Research, the study's senior author for gene discovery. “We're still a long way from understanding how this chromosomal deletion or duplication increases the risk for autism, but this is a critical first step toward that knowledge.”
Population studies indicate that up to 90 percent of cases of autism and what are referred to as autism spectrum disorders have some genetic component, but only 10 percent of cases can be attributed to known genetic and chromosomal syndromes. Since several of those conditions involve deletions or duplications of chromosomal segments – including an inherited deletion of a region of chromosome 15 – the investigators conducted a complete genome scan of samples from the Autism Genome Research Exchange, which contains DNA from families in which at least one child has autism or a related disorder.
The scan of more than 1,400 affected individuals and a similar number of their unaffected parents revealed that an identical region of chromosome 16 was deleted in 5 individuals with an autism spectrum disorder but not in any of the parents, implying that the deletion had occurred spontaneously and was not inherited. To confirm this observation, clinical testing data from almost 1,000 patients from Children's Hospital Boston – about half of whom had been diagnosed with autism or a related developmental delay – was evaluated. Among those with a developmental disorder, 5 children had the same deletion, and in another 4 the chromosome segment was duplicated. Again, no abnormalities were seen in DNA from children without autism or developmental delay.