Abstract
A consortium of researchers from the University of California, San Francisco (UCSF), Rutgers University, Massachusetts General Hospital, the University of Florida, and Yale School of Medicine have used whole-exome sequencing (WES) and de novo variant detection to explore the genetics underlying Tourette syndrome, a neurological condition characterized by vocal and physical tics.
Following an approach that has been used to study the genetic causes of autism, the consortium found that Tourette syndrome, like autism, is the result of multiple gene mutations. About 400 risk genes were identified in the consortium’s study, which focused on de novo variants—rare genetic mutations that are not inherited from parents, but rather occur spontaneously at conception.
Of the 400 risk genes, four looked particularly disruptive. One gene that is considered particularly “high risk” is WWC1, also called KIBRA (for KIdney- and BRAin-expressed protein). This gene, which is involved in brain development, memory, and the brain’s response to the hormone estrogen, appears to have a greater than 90% probability of contributing to Tourette syndrome.
Additional details appeared May 3 in the journal Neuron, in an article entitled “De Novo Coding Variants Are Strongly Associated with Tourette Disorder.” The authors of the Neuron article said they hope that their findings will help uncover the genetic and brain pathways that cause the disorder and enable the development of more effective treatments.
“We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total),” wrote the authors of the Neuron article. “We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants.”