Sufferers of Gilles de la Tourette syndrome are plagued by unwanted movement and verbal tics that range from extra winks and Grimaces involuntary grunts or even curse. Although the disease tends to run in families, little is known about its genetic basis. The researchers found a mutated gene that seems to cause the disorder in a family with nine extremely rare sufferers. While this mutation is the cause of most cases of Tourette's syndrome, it can push researchers to study treatment and potential mechanism they otherwise would not have considered.
Since the French neurologist Georges Gilles de la Tourette first described its namesake state 125 years ago, scientists have puzzled over the cause. Many recent attention has focused on a brain region called the basal ganglia, which is involved in repetitive behaviors and the neurotransmitter dopamine. In 05, a team led by child psychiatrist and geneticist Matthew State of the School of Medicine at Yale University, reported one of the first genetic clues to disease, a mutation in a gene called SLITRK1 seems to be responsible for a rare handful of cases. But the function of SLITRK1 and its contribution to Tourette syndrome is still largely a mystery.
In the new study, the State and his colleagues examined a family in which the father and eight children (six son and two daughters) have the syndrome. Many genetic detective work led them to a mutation in a gene called HDC , which encodes L-histidine decarboxylase, an enzyme involved in the production of histamine, a signaling molecule with a wide variety roles in the body. The same mutation was present in all members of the family who had Tourette's, but was absent in the thousands of DNA samples from control subjects, which included non-related people of similar ethnic backgrounds, as well as a group of 720 Tourette patients, the researchers report today in the New England Journal of Medicine . The mutated version of HDC Genes likely results in a truncated version of the enzyme, which would result in reduced levels of histamine, State said.
histamine may be best known for her role in triggering sneezing and itchy eyes during allergy season, but it also functions as a neurotransmitter in the brain. Exactly how histamine abnormalities contribute to the symptoms of Tourette's syndrome is unclear, but the State notes that knocking out the equivalent of HDC gene makes mice more prone to bobbing head, spinning, and other repetitive behaviors. In addition, he said, there is evidence that some histamine receptors cluster in the basal ganglia and the signaling of histamine can act as a brake on the signaling of dopamine.
"They make a very convincing argument that this mutation in this family is responsible for Tourette's," says Jon McClellan, a psychiatrist at the University of Washington, Seattle. "If histamine is actually an active player in Gilles de la Tourette syndrome, it would really open a new way of treatment" involving drugs that stimulate histamine, says Jeremiah Scharf, a behavioral neurologist and the Neurogeneticist Harvard Medical School in Boston. But he warned that much more work is needed to determine if the results of this family can be leveraged to help thousands of other people with the disorder.
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