Researchers find the genes responsible for Tourette's syndrome in children

August 11, 2017
Chromosome rearrangements deletions and duplications -- mean that the number of copies of different genes varies and can be unique to each person. Credit: MIPT's Press Office

An international research team including Vasiliy Ramensky, a member of the MIPT Life Sciences Center, has unraveled genetic characteristics that increase the risk of developing Tourette's syndrome. Tourette's is a central nervous system disorder that is often inherited. The scientists compared genetic data of thousands of people with Tourette's and healthy people, and found that in people with the condition, there are significant modifications in two genes—NRXN1 and CNTN6. The paper detailing their study was published in the journal Neuron.

Tourette's syndrome is characterized by motor and vocal tics, and it manifests itself in childhood. Patients often make uncontrolled movements and sounds (including swear words in 10 percent of cases). The tic impulse is described by patients like a growing tension that has to be released, very similar to the urge to sneeze. Tourette's is not a rare disease. It is found among 0.3 to 0.9 percent of the population, and the children of those who suffer Tourette's are 60 times more likely to have it as well. However, the syndrome can also appear in children with no family history of the condition. About 85 percent of patients suffering from Tourette's have co-occurring conditions, such as obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism spectrum disorders, anxiety and depression. The fact that the mechanisms of these illnesses and Tourette's syndrome converge means that Tourette's studies can shed light on the causes of other mental disorders.

It is believed that Tourette's syndrome is a developmental disorder of the brain and nervous system. This is partially proven by the fact that the symptoms appear in childhood and peak during adolescence. However, the exact causes are unknown. There is no doubt that the disorder is of a predominantly genetic nature, but the particular that increase the likelihood of developing Tourette's have not yet been identified. Candidate regions found in different research studies rarely coincide. This suggests that the condition is caused by a combination of genetic factors—in other words, it has complex genetic architecture.

Modern genetic studies focus on searching for point mutations and significant genetic rearrangements. Significant rearrangements in the genome, which are called copy number variations (CNV), can lead to deletion, gene fragment loss, or to gene duplication with repeat chromosome regions. The number of gene copies in an individual genome affects the quantity of protein encoded by the gene: the more copies, the more protein. However, not all chromosome rearrangements affect vital gene segments and not all of them are related to diseases.

The researchers studied the of 2,434 people with Tourette's syndrome and 4,093 (the control group). The scientists catalogued all deletions and duplications in each genome and classified them according to frequency, length and whether they affect genes or not. They found rare and long chromosome rearrangements affecting genes, more often on average among the people with the disorder than among people from the control group. This suggests that these types of chromosome rearrangements have particular clinical utility. The researchers then identified which genes suffer the most from these rearrangements. It was found that people with Tourette's frequently had significantly more deletions in the NRXN1 gene and duplications in the CNTN6 gene. Proteins encoded in these genes (neurexin 1 and contactin 6) are involved in the process of cell fusion in the nervous system.

Deletions affecting NRXN1 have already been described in papers on other mental , in particular, schizophrenia. The link between deletions in NRXN1 and Tourette's syndrome has already been shown in earlier studies in a small sample of cases. It is now safe to say that this type of genome variation increases the risk of developing the condition. Duplications in CNTN6 were linked to Tourette's for the first time, though deletions affecting this gene have already been noticed in cases of .

Vasily Ramensky, a member of the Genome Engineering Lab of MIPT's Life Sciences Center, comments: "Gradually, step-by-step, we are gathering information about the genetic architecture of Tourette's . In this paper, we have made an essential step in this direction, as it is now statistically proven which genomic changes in the genes discovered are linked to the predisposition to the condition. This gives the opportunity to provide better diagnoses. Our next step is to work out how such rearrangements in the found genes affect cell operation. Understanding these mechanisms will help in finding new therapies."

Explore further: Rare genetic variants found to increase risk for Tourette syndrome

More information: Alden Y. Huang et al, Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome, Neuron (2017). DOI: 10.1016/j.neuron.2017.06.010

Related Stories

Rare genetic variants found to increase risk for Tourette syndrome

June 21, 2017
An international research team led by investigators at Massachusetts General Hospital (MGH) and the University of California at Los Angeles (UCLA) - along with their facilitating partner the Tourette Association of America ...

Tourette-like tics vanish in mice treated with histamine

June 6, 2017
Yale scientists produced increased grooming behavior in mice that may model tics in Tourette syndrome and discovered these behaviors vanish when histamine—a neurotransmitter most commonly associated with allergies—is ...

Elevated rate of autism symptoms found in children with Tourette syndrome

June 22, 2017
Around one in five children with Tourette syndrome, a neurological disorder characterized by involuntary movements and vocalizations, met criteria for autism in a study headed by UC San Francisco. But this prevalence may ...

Do children with Tourette syndrome have an advantage at language?

September 29, 2016
Children with Tourette syndrome may process aspects of language faster than other children, a new study shows.

First clear-cut risk genes for Tourette disorder revealed

May 3, 2017
Tourette disorder (also known as Tourette syndrome) afflicts as many as one person in a hundred worldwide with potentially disabling symptoms including involuntary motor and vocal tics. However, researchers have so far failed ...

Researchers find rare genetic cause of Tourette syndrome

January 9, 2014
A rare genetic mutation that disrupts production of histamine in the brain is a cause of the tics and other abnormalities of Tourette syndrome, according to new findings by Yale School of Medicine researchers.

Recommended for you

New approach to studying chromosomes' centers may reveal link to Down syndrome and more

November 20, 2017
Some scientists call it the "final frontier" of our DNA—even though it lies at the center of every X-shaped chromosome in nearly every one of our cells.

Genome editing enhances T-cells for cancer immunotherapy

November 20, 2017
Researchers at Cardiff University have found a way to boost the cancer-destroying ability of the immune system's T-cells, offering new hope in the fight against a wide range of cancers.

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

US scientists try first gene editing in the body

November 15, 2017
Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person's DNA to try to cure a disease.

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.