A new study examines the DNA mutations that may interfere with brain development in Tourette's syndrome.
In the United States, about 200,000 individuals now live with Tourette's syndrome in its most severe form.
The neuropsychiatric condition is characterized by involuntary and repetitive movements or sounds called tics.
We do not yet know the precise cause of Tourette's syndrome. However, researchers have linked it with abnormal development of certain brain areas, including the basal ganglia, the frontal lobes, and the cortex.
Also, brain networks that connect these regions — along with neurotransmitters such as dopamine and serotonin — have also been linked to the condition.
Now, researchers bring new insights into what might disrupt the brain development in Tourette's syndrome, and they have published their findings in the journal Cell Reports.
Sheng Wang, who is affiliated with the National Institute of Biological Sciences in Beijing, China, and the Department of Psychiatry at the University of California in San Francisco, is the recent paper's first author.
Studying the genes involved in Tourette's
Wang and his colleagues worked on the largest genetic study of Tourette's syndrome: the Tourette International Collaborative Genetics (TIC Genetics) study.
"Through the initial families who participated, we were able to collect samples and data to start the study and establish the first sharing repository for researchers from all over the world interested in studying Tourette syndrome," reports study co-author Gary Heiman, an associate professor in the Department of Genetics at Rutgers University–New Brunswick in New Jersey.
The newly published paper represents the second major set of results from the TIC Genetics study, which has spanned over 11 years.
The first set of results was published last year and revealed four genetic mutations that could be responsible for the disruptions in brain development noticed in Tourette's.
At the time, the researchers had analyzed 511 genetic trios. In the new study, they performed whole-exome sequencing of an additional 291 trios, and they carried out an analysis of the combined 802 genetic trios.
Genetic mutations and cell development
The analysis found that copy number variants (CNVs), or chromosomal variations that involve larger portions of DNA and which may span over several genes, can trigger Tourette's syndrome. CNVs alter the number of copies of DNA regions by duplicating and deleting them.
Study co-author Jay Tischfield, from Rutgers University–New Brunswick, explains, "We discovered that CNVs occur two to three times more often in children with Tourette syndrome compared to those without."
The investigators also uncovered a "high-confidence" risk gene called CELSR3, whose harmful mutations were found in several families.
Lastly, they also found de novo mutations in genes that "encode proteins involved in cell polarity." Cell polarity describes "the intrinsic asymmetry" that is observed in the "shape, structure, or organization" of cells.
Cell polarity is key for the development and specialization of cells. The mutations revealed help illuminate the brain development issues that are present in Tourette's.
Overall, the scientists approximate that over 400 gene mutations, either singular or combined, could increase the risk of Tourette's syndrome.
"These [...] significant findings," claims Tischfield, "provide a framework for future research into the causes and treatment of this remarkable and peculiar disorder."