Rare Genetic Mutation Linked to Autism
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HealthDay News — Researchers say they've discovered a new genetic cause of autism, singling out a rare gene mutation that appears to hamper normal brain development early on in powerful ways.
The gene, CTNND2, provides instructions for making a protein called delta-catenin, which plays crucial roles in the nervous system, said senior author Aravinda Chakravarti, PhD, a professor in the Johns Hopkins University School of Medicine's Institute of Genetic Medicine.
His research team found that a group of girls with severe autism carried CTNND2 mutations that appeared to reduce the effectiveness of delta-catenin, potentially affecting their neurological development.
“There are many, many proteins that in fact 'moonlight,' doing many, many different things," Chakravarti said. “Maybe the severity of the effect of delta-catenin comes from the fact that when you lose function of this protein, you lose not just one function but many functions. Although that remains to be shown, it is strongly implicated by our study.”
The researchers discovered the CTNND2 gene's link to autism using an approach that focuses on rare and extreme cases of autism, according to the study released online in the journal Nature.
By focusing on extreme cases, they believe they will discover genes that have a more powerful effect on brain development and help explain the root causes of autism.
The genetics of 13 girls with autism were sequenced, and then compared to genes carried by people who did not have autism who were listed in a public database. The investigators detected four potential culprit genes for autism, including CTNND2.
The researchers zeroed in on CTNND2 because it has been linked to another developmental disorder called cri-du-chat syndrome, Chakravarti said.
Many people with cri-du-chat syndrome lack a copy of the CTNND2 gene in each cell, and this appears to cause severe intellectual disability, according to the U.S. National Institutes of Health.
Chakravati A, et al. Loss of δ-catenin function in severe autism. Nature. 2015; doi:10.1038/nature14186.