Genetic Breakthrough
Yields Clue to Tourette Syndrome
BAYSIDE, NEW YORK – OCTOBER 11, 2005 – In what is being
called a significant breakthrough in understanding the genetic
underpinnings of Tourette Syndrome, researchers have identified a
gene mutation that appears to lead to this neurological disorder in
some individuals.
In a paper published in the October 14, 2005 Science
magazine, (a publication of the American Association for the
Advancement of Science), Vol.310 (#5746) pp 317-320, findings were reported by a team led by Dr.
Matthew State, Assistant Professor of Child Psychiatry and Genetics,
Yale University School of Medicine and Child Study Center. Pursuing
genetic analysis of one boy with TS with a known chromosomal
abnormality, the group was able to pinpoint a gene (SLITRK1) on
Chromosome 13 that is associated with some forms of TS. This gene is
expressed in several areas in the brain—specifically the cortex and
basal ganglia—the same brain regions previously implicated in
causing TS symptoms. When functioning normally, this gene is
involved with the growth of neurons in these regions. In other
affected individuals, two additional rare abnormalities in this gene
were identified. (click
here to
read Science magazine commentary and paper).
Dr. State’s group was able to then
confirm their findings in a number of ways: by performing several
additional tests on non-affected relatives (the initial mutation was
not found), and by determining that none of the abnormalities
identified in patients were present in many thousands of chromosomes
from unaffected individuals. Additional testing in cell cultures
showed that the genetic changes identified altered protein function
or expression. Taken together, these converging results suggest that
this gene is associated with some forms of TS in some families.
The national Tourette Syndrome
Association (TSA) has provided substantial funding for a significant
number of TS genetic studies for over two decades.* It now appears
that after many years of support, a critical discovery has been
made.
The Association and its Board of
Directors has already moved quickly and approved additional support
to continue this work.
Last year Dr. State was awarded the
TSA Early Career Research Award for his work toward identifying the
genes involved in TS. At that time, TSA funding also was awarded to Nenad Sestan, MD, Ph.D. a co-author on the paper.
With this additional TSA funding,
Drs. State, Sestan and colleagues will now pursue the development
and investigation of a mutant mouse where the suspect gene has been
inactivated. Development of such a “knock out” mouse will allow the
team to examine the impact of this gene mutation on normal brain
development.
“While not a cure, TSA’s funding of
this effort is not only a logical ‘next small step,’ but it is also
potentially a ‘giant leap’ for the broader field of TS science, and
especially for the long-standing efforts by scientists to identify
the causes of, and improved treatments for this disorder,” said Dr.
Neal Swerdlow, Chair of TSA’s Scientific Advisory Board and
neuropsychiatrist at the University of California, San Diego, School
of Medicine.
Through newsletter articles and
subsequent advertising for families with known chromosomal
abnormalities, the TSA was able to locate and then refer the family
that proved critical to this study to Dr. Carol Mathews (UCSD) who
did a comprehensive assessment of the family. She in turn forwarded
that information on to Dr. David Pauls (MGH) who knew that Dr.
State’s lab was performing studies on chromosomal abnormalities in
TS. Both Drs. Mathews and Pauls are members of the TSA International
Consortium for Genetics. Monte Redman, TSA Chairman, said, “We are
particularly gratified by the fact that, ultimately, this close
collaboration among TS scientists bore such valuable fruit.”
Dr. State commented, “TSA has been
indispensable in helping us in our research on Tourette Syndrome.
The Association has always been extremely encouraging to me and my
research and has continually worked hard to insure that relevant
patients are brought to my attention and sent to my lab. Finding
these kinds of specific patients is like finding a needle in a
haystack, and without the TSA, we would never have gotten this
lead.”
Marked by involuntary twitching and
vocal tics, TS is an inherited, neurobiological disorder frequently
misunderstood and misdiagnosed, affecting more than 200,000
Americans. TSA is a national voluntary organization comprised of a
network of 35 chapters with over 300 support groups across the
country. For more information on TS, call 1-888-4-Touret and visit
http://tsa-usa.org
*Major support for Dr. State’s laboratory and this work was provided
by the NIH/NINDS and several other funding sources.
Tourette Syndrome Association, Inc. / 42-40 Bell Boulevard / Bayside NY 11361 / 718-224-2999 / © 2000-2005