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Researchers at Yale identify a genetic link to Tourette’s Syndrome


In what may be a major milestone in Tourette’s Syndrome (TS) research, scientists at Yale School of Medicine and their colleagues have identified a gene called SLITRK1 that appears to contribute to some cases of TS, according to a report in the October 14 issue of Science.

"We now have rare mutations, expression and functional data, all supporting a role for this gene in Tourette’s Syndrome," said senior author Matthew State, M.D., Harris Assistant Professor in the Yale Child Study Center and in the Department of Genetics at Yale. "This finding could provide an important clue in understanding Tourette’s on a molecular and cellular level. Confirming this, in even a small number of additional TS patients, will pave the way for a deeper understanding of the disease process."

TS is a relatively common neurological disorder characterized by tics--involuntary, rapid, sudden movements or vocalizations that occur repeatedly in the same way. It affects as many as one out of 100 school age children. The tics begin in mid-childhood and peak at the start of adolescence. TS is not life threatening, but affected children commonly have other neuropsychiatric disorders including ADHD, obsessive-compulsive disorder or depression. State said TS patients swearing uncontrollably is actually uncommon, with only a small percentage of TS patients ever having this symptom.

For years, many researchers sought a single, abnormal gene for TS. Since none was found, it was concluded that multiple genes either cause or contribute to the disorder. While many researchers looked for genetic similarities among large groups of TS patients, State and his team took the opposite approach pioneered by co-author and Yale’s Chair of Genetics, Richard Lifton, M.D., of searching for unusual patients with TS. With help from the Tourette Syndrome Association, they found such a case in which a child had TS and carried a chromosomal abnormality.

Working with Yale neurobiologists and co-authors Nenad Sestan and Angeliki Louvi, the team used molecular methods to identify differences in that child’s DNA. In particular, they found one gene expressed in the brain near the chromosomal break point. They compared the gene to a wider TS population of 174 people. The team found an abnormal DNA sequence in one family and the identical, very rare change in the DNA sequence in two unrelated people. This second finding was in a non-coding region of the gene that does not directly make protein.

A lead author on the study, graduate student Kenneth Kwan made the key observation that this segment of the gene was likely to be involved in gene regulation through the interaction with small molecules called microRNAs. In a series of experiments, the research team found that this was indeed the case.

Karen N. Peart | EurekAlert!
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