Rare mutations in two genes that significantly increase the risk of developing Tourette's syndrome have just been identified. In the long run, the discovery paves the way for the development of new therapeutic strategies for patients.

Tourette's syndrome is a neurological condition affecting 1 person in 100. It is characterised by involuntary and uncontrollable movements (such as jerking of the head and jumping up and down) and vocal tics (such as grunting, coughing or shouting out words).

Patients often experience the first symptoms in childhood, but continue being affected as adults. Tourette's syndrome is often associated with a range of other conditions, such as obsessive compulsive disorder or attention deficit hyperactivity disorder.

But very little is known about what causes the condition, for which there is still no cure. Past studies have suggested that the condition is highly genetic - but this genetic component appears to be very complex.

Indeed, multiple genes, different from one patient to the next, may be involved. To date, only a couple of genes have been linked to Tourette's syndrome, but many of these associations were not considered to be very robust.

On the path to treatment

In a study now published in the journal Neuron, scientists present their analysis of the genome of 2,434 people of European ancestry diagnosed with Tourette's syndrome, comparing them with 4,093 healthy individuals with the same ancestry.

The genetic data of the participants was obtained through the Tourette Syndrome Association International Consortium for Genetics (TSAICG) and the Gilles de la Tourette Syndrome GWAS Replication Initiative.

The scientists identified a number of rare mutations — either deletions or duplications of genetic material — in two genes called NRXN1 and CNTN6. Both these genes are involved in neurodevelopment, as NRXN1 plays a role in the development of synapses that transmit signals between neurons and CNTN6 is involved the development of neuronal connections involved in movement control.

The identification of these mutations does not completely answer the question of what causes Tourette's syndrome, but this is perhaps the most significant association between rare genetic variants and the disorder to date.

If more research was conducted to better understand how the two genes function, it could help scientists identify exactly which cells in the brain are not functioning correctly at which specific times and it would put them on the path to finding new treatments.

"This is a first, key step in understanding the role of these genes in the disease process and ultimately in pointing the field toward possible therapeutic strategies," said Dr. Giovanni Coppola, a professor of psychiatry and neurology at UCLA's Semel Institute for Neuroscience and Human Behavior, and the study's co-senior author. "All of us in the field have been trying to understand which genes increase the risk of disease."

The study was funded by the Tourette Association of America, the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS). It is the largest ever to analyze genetic structural variants or copy-number variants (CNVs) of Tourette.