Researchers at the Yale School of Medicine are the first to show that a mutation to a single gene can cause Tourette Syndrome (TS).

While a previous Yale study showed that a mutation to the histamine-producing gene HDC co-occurred with TS, the study published in the journal Neuron on Jan. 8 demonstrated a causal link between the two. The study did not examine why the change in histamine causes TS — a condition characterized by involuntary motor and vocal tics — but the discovery promises new approaches to treat Tourette’s and possibly other disorders, said Christopher Pittenger ’94, study author and professor of psychiatry in the Yale Child Study Center.

“Every time there is a genetic finding in a disorder it’s important to keep in perspective that not any one genetic finding will lead to a cause or a cure,” said Thomas Fernandez MED ’05, a professor in the Yale Child Study Center. “This gene is ‘a’ cause, not ‘the’ cause for Tourette’s, but it is one piece in the bigger puzzle to help us treat and medicate which is really the main point for doing genetic research — medication.”

In 2010, Yale researchers identified the connection between a mutation in the histamine-producing gene and TS when they found the particular mutation prevalent in a Washington state family where nine out of 10 members had TS. To show that the mutation causes TS and did not just co-occur, Pittenger’s research team engineered mice with the HDC mutation, which inactivated the enzyme produced by the HDC which goes on to produce histamine. The mice with the mutation displayed tics when stimulated with minor doses of amphetamine, unlike those without the mutation.

While the results in mice demonstrate that a mutation in the HDC gene causes TS, Fernandez, one of the authors of the 2010 study, said there are other environmental causes of TS and may likely be other genetic causes of the disorder. According to Yale Child Study Center professor James Leckman, environmental factors such as inflammation, infection and stress can induce symptoms of TS.

“There often occurs a waxing and waning of symptoms,” he said. “The types of motor and vocal tics are quite diverse and in the short run are very sensitive to excitement and anything exciting or stressful.”

While the study does not explore the mechanism connecting histamine dysfunction to TS, Pittenger said the relationship between histamine and dopamine may be central. Researchers noticed that changes in histamine levels corresponded to those of dopamine, a neurotransmitter that plays an important role in movement.

There has been little progress in treating TS over the last decade, and Leckman said identifying histamine as key in TS provides possible hope for what next steps to take. Leckman added researchers are developing drugs that target a particular histamine receptor that holds promise for alleviating TS symptoms.

The research team hopes that efforts to treat TS will also help treat disorders that are often co-occurring, including OCD and ADHD.

“Higher rates of tics are present with developmental OCD and ADHD,” said Michael Bloch MED ’04, professor in the Child Study Center. “Children with Tourette’s have an extremely high risk factor because a third of kids will go on to develop OCD compared to a maximum of 3 percent of the general population.”

Tourette’s affects 1 percent of the population and is most severe and common in boys ages 8–12 beginning around 6 years of age.