Developmental and behavior problems in individuals with autism associated DNA imbalance characterized

Researchers at Signature Genomic Laboratories, which performs diagnostic genetic testing of chromosome abnormalities in individuals with unexplained physical and developmental disabilities, including autism, recently characterized a broad spectrum of developmental and behavior problems in individuals with a DNA imbalance that has been associated with autism.

Although the causes of autism are not well understood, it has long been established that genetic predisposition is a primary determinant of susceptibility to autism. Recent searches for genetic aberrations in large populations of individuals with autism or an autism spectrum disorder (ASD) have identified missing or extra copies of a small portion of DNA on chromosome 16 in a few of these individuals.

In their study, published in the Journal of Neurodevelopmental Disorders, geneticists at Signature Genomics worked from the other direction, examining the clinical features of 45 individuals with loss of the region on chromosome 16, and 32 individuals with an extra copy of the region, out of 9,773 individuals referred to their laboratory for testing. Of the 16 individuals with the deletion old enough to be evaluated for autism, all had below-average intelligence, and a majority had speech or language problems or delays and various behavioral problems. Nine of the 16 individuals had speech and behavior profiles that aroused clinical suspicion of ASD; five had formal evaluations, and three had pervasive developmental delays. The remaining seven individuals had behavior problems that were clearly distinct from ASD, and several were specifically reported to be social without any stereotypic behaviors. A majority of individuals with the duplication had delayed development and/or specific deficits in speech or language, although these features were not as consistent as seen with the deletions of the same region. Based on these findings, the authors suggested the abnormalities on chromosome 16 are associated with a spectrum of developmental and speech delays and behavioral issues that encompasses autism and other neurological problems.

“Whereas most studies that have implicated DNA imbalances at this region on chromosome 16 have examined populations of individuals with clear indications of autism, we took a unique, ‘genotype-first’ approach by first identifying individuals in our vast patient database with the same genetic constitution, or genotype, and then examining them for common clinical features. This allowed us to show that abnormalities of this region are not unique to autism but likely play a role in more general neurodevelopmental problems,” said Dr. Blake C. Ballif, Ph.D., Director of Product Development and Research at Signature and senior author of the study. “These promising results should aid diagnosis and research of individuals with abnormalities of this region on chromosome 16.”