Significant Breakthrough as Genes Involved in Tourette Syndrome Identified

Tourette syndrome is characterized by involuntary motor and vocal tics with an incidence of one in hundred individuals worldwide. The cause behind this disorder has not been determined so far, but a study by scientists from the Rutgers University, Massachusetts General Hospital, Yale School of Medicine, UC San Francisco and the University of Florida, detailed the identification of genes associated with the development of the condition. The study was published in the journal Neuron. This is a significant step towards identifying the mechanism of disease development which could be used for better therapeutic strategies. The study helped in identifying

• The first “high-confidence” gene that was found to increase the risk of Tourette syndrome
• Three other probable risk genes

Co-senior author of the study, Dr. Mathew State, who is a distinguished Professor and chair of the Department of Psychiatry at UCSF, said that he was repeatedly confronted with patients and families who experienced frustration because of the poor understanding of the condition. According to Dr. State, the current study is a major initial step into identifying risk factors, using the latest genomic technologies.

Rare Variants to Identify Mechanism

The scientists had previously used similar techniques to identify the genetic basis of autism spectrum disorders, resulting in considerable advancements in autism research over the past five years.

In order to identify rare variants, the regions of the genome that code for protein were compared between Tourette affected children and their parents. This step was carried out to identify new variations or mutations that are not transmitted from parents, but those that occur at conception. The biological effects of denovo variants or spontaneous variants are stronger than effects of variants that have been passed down generations.

Dr. Jeremy Willsey who is the co-author of the study said that if the genes under study were found to increase the risk for Tourette’s syndrome, they could then be used to develop better treatment methods.

Analyzing Genomic Data

The genomic data was analyzed by the research team

• There were a total of 311 "trios" that comprised children who had Tourette disorder and their parents who were mostly free from the disorder.
• The analysis showed a strong association between de novo signaling and the disorder.
• A replication study was carried out on 173 trios and the same results were obtained.

The results of the study showed that

• 12 % of Tourette disorder cases involved de novo variants.
• The de novo variants affected nearly 400 different key risk genes.

Key Genes Associated With Tourette Disorder

The genetic data from the two studies were combined, which led to the identification of four genes expressed in the brain that were significantly associated with this disorder.

• WWC1: also known as KIBRA had a 90% probability of being associated with Tourette’s disorder. This gene is known to be  involved in brain development, the brain’s response to estrogen and memory.
• FN1 and CELSR3: These are involved in brain circuitry development.
• NIPBL or Delangin: NIPBL is involved in gene expression regulation in the brain.

These last three genes have a 70% probability of resulting in the disorder.
NIPBL gene is also involved in the development of

• Obsessive-compulsive disorder
• Cornelia de Lange syndrome
• Anxiety
• Attention deficit/hyperactivity disorder

The study was successful in identifying genes involved in Tourette syndrome due to the collaborative efforts of researchers and clinicians, re-inforcing the need for collaborative science and access to open data.

Tourette Syndrome

This is a neurological disorder which is characterized by classic symptoms of repetitive and involuntary movements, along with vocalizations called tics. It is named after Dr. Georges Gilles de la Tourette, who was a leading French neurologist and who first described the condition in an old woman.

The symptoms are initially identified between 3 and 9 years and usually occur more often in males than in females. 50% of the patients may also have attention deficit hyperkinetic disorder. The voice tics include throat clearing, snorting, sniffing, squeaking, grunting, sucking, puffing, barking and other sounds. These tics are increased during periods of excitement and lowered when carrying out an activity or sleeping.

• 200,000 Americans have a severe form of Tourette syndrome
• One in a 100 people worldwide have mild symptoms

The identification of the genes that are found to be involved in Tourette’s syndrome will help in developing effective treatment methods.

References:

1. Tourette Syndrome Fact Sheet - (http://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2011;volume=53;issue=1;spage=66;epage=68;aulast=Raj)
2. Tourette's disease with impulse control disorder - (https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Tourette-Syndrome-Fact-Sheet)

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Source-Medindia