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Study: Gene May be Linked to Tourette (Oct 2005)

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  • Study: Gene May be Linked to Tourette (Oct 2005)

    Gene may be linked to Tourette's Syndrome
    Thu Oct 13, 2005 7:02 PM BST

    Source Reuters

    WASHINGTON (Reuters) - Researchers said on Thursday they have found a gene that helps cause Tourette's Syndrome, but that many other genes are also likely to be involved in the complex disorder.

    Tourette's may affect as many as one in 100 people and is marked by muscle and vocal tics including repeated sudden movements or vocalizations. Children with Tourette's also often have attention deficit hyperactivity disorder, obsessive-compulsive disorder or depression.

    In a report published in Friday's issue of the journal Science, Dr. Matthew State of the Yale University School of Medicine and colleagues at several other institutions said a gene called SLITRK1 appears to contribute to some cases of Tourette's.

    "This finding could provide an important clue in understanding Tourette's on a molecular and cellular level," State said in a statement.

    "Confirming this in even a small number of additional TS patients will pave the way for a deeper understanding of the disease process."

    State and colleagues looked for unusual patients with a clear genetic anomaly.

    They found a boy who was the only member of his family with Tourette's, and who had a gene inversion on chromosome 13. A gene inversion occurs when a section of chromosome appears to have broken off and flipped before being reinserted.

    Looking at the ends of this section, the researchers found one gene, called SLITRK1, that is active in brain cells and is associated with the growth and interconnection of neurons.

    Then they screened 174 more people with Tourette's, comparing their SLITRK1 gene to the version found in people who do not have the syndrome, and found a genetic mutation.

    This one gene variation is unlikely to hold all the answers to Tourette's, State said.

    "I think there is general consensus at this point that there are likely to be multiple genes, likely interacting, and probably different sets of genes in different people, that contribute to TS," he said.

    Dr. Matthew State, Assistant Professor of Child Psychiatry and Genetics of the Yale University School of Medicine and Child Study Center, was awarded the TSA Early Career Research Award, for his work toward identifying the genes involved in TS. Dr State used cytogenetic techniques and concluded that rearrangements of small pieces of genetic material on chromosomes 13 and 18 were associated with TS. It is the first time that such an award has been made.
    4th International Scientific Symposium on Tourette Syndrome held in Cleveland, OH from June 25-27, 2004
    TouretteLinks Forum

  • #2
    Study: Gene May be Linked to Tourette (Oct 2005)

    This is exciting if it can be used to diagnose Tourette going forward some day. It would make the diagnostic process much quicker. The history and then a test to confirm.

    TSFC Homepage


    • #3
      Study: Gene May be Linked to Tourette (Oct 2005)

      October 14, 2005

      Scientists have identified a gene defect unique to a small percentage of people with Tourette syndrome, the complex brain disorder that triggers involuntary movement and speech.

      The discovery, detailed today in the journal Science, was led by researchers at Yale University and included contributions from a San Diego expert on the condition.

      Most efforts to understand Tourette syndrome have focused on imaging the brains of patients and examining animal physiology. So pinpointing a human gene that underlies the abnormalities scientists have observed is significant.

      "Even if we find something that's responsible in a tiny fraction of people with Tourette, it may . . . open up new opportunities to find other genes involved or to understand mechanisms of (the) disease," said Dr. Matthew State, the head researcher and an assistant professor for Yale's Child Study Center and genetics department.

      "That's really where we hope the payoff will be."

      State and his colleagues found that a mutation in the gene SLITRK1 seems to play a role in about 1 percent to 2 percent of all Tourette syndrome cases.

      Scientists first identified SLITRK1 in the fruit fly drosophila, and they have also found it in mice. The study described today marks the first time researchers have studied the gene directly in humans, said Dr. Carol Mathews, a Tourette syndrome expert at University of California San Diego who helped with the study.

      "This is a gene that hasn't been really looked at in humans before," Mathews said.

      Until now, scientists had been unable to link specific genes to the disorder, State said. The SLITRK1 theory must be verified as well.

      Dr. Neal Swerdlow, a Tourette syndrome researcher at UCSD who did not participate in the study, called the work "potentially a giant leap for the broader field of (Tourette syndrome) science and especially for the long-standing efforts by scientists to identify the causes of, and improved treatments for, this disorder."

      Swerdlow chairs the scientific advisory board of the New York-based Tourette Syndrome Association, which helped find the boy whose DNA the researchers studied as part of their project.

      Scientists believe many genes are involved in the onset of Tourette syndrome, and that environmental factors such as abnormal brain development during gestation, hypoxia at birth and streptococcal infection in childhood might trigger genes that lead to the disorder.

      "Invariably there's not only going to be a bunch of genes out there to discover, but there also are going to be important gene-environment interactions," State said. "What we're hoping is that by having even one small thread to pull on, we can at least begin to then have a notion about where to look for some of these other guys."

      Tourette syndrome typically shows up in children 5 to 18 years old, sometimes in conjunction with conditions such as obsessive-compulsive disorder and attention deficit hyperactivity disorder, the association said.

      Its symptoms include tics such as excessive blinking of the eyes, jerking of the head, shrugging of the shoulders and facial grimaces. People who suffer from the syndrome may also clear their throat, sniff and click their tongues repeatedly. Less than 15 percent of people with the disorder spontaneously blurt obscene language ? contrary to how Tourette's is often portrayed on television and in the movies.

      About one in 100 schoolchildren show symptoms of Tourette syndrome. All races and ethnic groups are affected. Parents who suffer from the disorder have a 50 percent chance of passing on to their children genetic defects that could cause the syndrome. Sons are three to four times more likely than daughters to exhibit the condition.

      The disorder ? named for the French neurologist Georges Gilles de la Tourette who first described the condition in 1885 ? is mostly a mystery. But scientists have amassed evidence that symptoms stem from a defect in the way the brain metabolizes a chemical called dopamine.

      Treatment during the past 40 years has focused on drugs that attempt to normalize the activity of dopamine and other related chemicals in a deep-seated region of the brain called the basal ganglia.

      "Finding a genetic basis will help us to understand what has gone wrong in the brain," Mathews said. Success on this front might lead to genetic tests that could tell people whether they are susceptible to the disease so they can take steps to protect themselves from environmental triggers, she said.

      "Ultimately, we may actually be able to use our knowledge . . . to target treatments," Mathews said.
      TouretteLinks Forum


      • #4
        Study: Gene May be Linked to Tourette (Oct 2005)

        Additional Details
        Source: 24/7 Updates

        A new avenue for understanding Tourette syndrome, the complex disorder that causes muscle and vocal tics has been opened by researchers who have identified the first gene mutation associated with it.

        Till date, causes of Tourette syndrome (TS), which afflicts as many as 1 in 100 people, have eluded researchers as the disease appeared to be caused by subtle mutations in many genes.

        The findings were published in the October 14, 2005, issue of the journal Science with Matthew W. State of the Yale University School of Medicine as senior author of the paper. His research was supported by a Howard Hughes Medical Institute institutional award to Yale which had been used to support early research by promising scientists at Yale.

        Other co-authors at Yale included HHMI investigator Richard P. Lifton, and neurobiologists Nenad Sestan and Angeliki Louvi from the Yale Child Study Center. The Yale scientists also collaborated with researchers from the University of California San Diego, Harvard Medical School, University of Missouri-Kansas City, University of Alabama at Birmingham, Johns Hopkins University School of Medicine and Cincinnati Children?s Hospital Medical Center.

        "There has been an evolving hypothesis about Tourette syndrome being a much more complex disorder," State said. "I think there is general consensus at this point that there are likely to be multiple genes, likely interacting, and probably different sets of genes in different people, that contribute to TS." The complex phenotype of the syndrome, which is often associated with obsessive-compulsive disorder, attention deficit hyperactivity disorder, or depression has lead to the notion of multiple gene mutation origin of the disease according State.

        In order to search for a TS-related gene the same approach as used by Lifton to search for causative genes involved in cardiovascular, renal, and bone diseases was adopted. "We took a page from Rick?s playbook in that we looked for unusual patients who have an identifiable genetic anomaly that we could trace to TS," said State.

        A boy who was the only member of his family with TS and who had a gene inversion on chromosome 13 was then discovered by the researchers. This is usually the case

        when a section of chromosome is broken off and reshuffles or reassembles before reinserting itself back into the chromosome.

        State and his colleagues identified one gene, called SLITRK1 (for Slit and Trk-like family member 1), that is actively expressed in the brain and is associated with the growth and interconnection of neurons. The researchers screened 174 more people with TS, comparing their SLITRK1 gene to that of individuals without TS. They found one characteristic SLITRK1 mutation in affected members of one family that was absent in unaffected members. The mutation was however not found in another 3,600 chromosomes from people without TS that they analyzed.

        Another variant sequence within SLITRK1 was found in two people with TS, in a region of the gene that was not part of the direct blueprint for the SLITRK1 protein. "This was the strongest piece of genetic evidence in the research paper," said State. "We found two examples of exactly the same rare sequence change in a regulatory, non-coding region of the gene. And it was in two unrelated individuals with TS." Furthermore, the alteration which they called variant 321, was not found in 4,200 chromosomes from individuals without TS.

        Variant 321 was found to be located in a region of the genome predicted to be involved in regulating SLITRK1 activity by interacting with molecules called microRNAs.

        The researchers also found that a specific microRNA that regulates SLITRK1 binds to the genetic site of variant 321and both the SLITRK1 and the regulatory microRNA are expressed in regions of the brain believed to be involved in TS. Finally, when the researchers studied the function of SLITRK1 in cultures of neurons, they found that those with the normal gene showed longer connective branches, called dendrites, than did those with the mutation.

        According to Lifton, "Matt?s approach of looking for genetic outliers that contribute to the pathogenesis of Tourette?s represents a new approach that has great potential to provide an avenue into the pathways that underlie this disease."

        "The idea of looking for clues from chromosomal anomalies is a very powerful one that has paid off in this case," said Lifton. "The findings point for the first time to a pathway that appears to contribute to the pathogenesis of TS and enables further studies not only from a genetic perspective, but also from a pathophysiologic one."

        State felt that even though the pathway that has been identified could prove important in understanding TS, "it still remains to be demonstrated by other labs whether aberrations in this pathway have pathological consequences in TS. Then we?ll really pop the cork on the champagne, because this will give us an opportunity to begin to understand one pathway that -- while it may be responsible for only a small percentage of TS -- gives very concrete clues to disease mechanisms."
        TouretteLinks Forum