Linkage Analysis of Tourette Syndrome: Clinical Aspects

Grant Type
Basic
Grant Year
1990
Institution Location
NY
Institution Organization Name
University of Rochester
Investigators Name
Kurlan, Roger, MD

Following identification of the world’s largest kindred affected by Tourette’s Syndrome (TS) in 1984, clinical investigators at the University of Rochester and molecular genetics scientists at Yale University have teamed up in a search for the TS gene. We have studied several large families with TS using a technique referred to as pedigree linkage analysis, whereby comparisons are made between the presence and absence of TS and the pattern of genetic material found in blood samples. To date, nearly 400 members of two large kindreds have undergone systematic evaluations and more than 175 genetic locations have been analyzed. Although the gene has not yet been localized, we have been able to exclude more than 60% of the human genetic material. We anticipate that our systematic approach will prove successful in the near future. Our TSA funded research field expeditions for the linkage studies have provided us with a unique opportunity to see TS in its “natural environment” and to thereby gain a better understanding of its true clinical features. A variety of observations have essentially allowed us to redefine traditional views of this illness. We have found that fully 30% of subjects were unaware of tics noted by the examiners and less than 20% had sought medical care for their tic disorder. This information suggests that most cases of TS and related tic disorders are mild and therefore do not come to medical attention. In addition, we have found that the characteristics imply that TS and related tic disorders are probably much more prevalent than was thought. It has now become more widely appreciated that the milder forms of TS are common, affecting up to one person in several hundred. Results from our standardized neuropsychological testing indicate that approximately 50% of subjects with tics meet criteria for an attention deficit disorder or obsessive-compulsive disorder. Furthermore a substantial portion of family members unaffected by tics meet criteria for these behavioral disorders —supporting the notion that behavior disturbances in some TS family members may be the sole manifestation of the disorder. Localization of the gene for TS will clarify its clinical features, improve genetic counseling and provide clues to its underlying mechanisms which will help in the development of new therapies. Seed monies provided by the TSA Permanent Research Fund in 1984 and 1985 allowed us to gather sufficient pilot data to secure funding for our TS project from the National Institutes of Health (NIH). With NIH support from 1987 to 1990 our study progressed well. However, subsequent, severe budgetary limitations at NIH prevented renewed funding for our project and led to a major curtailment in our research efforts and a substantial budget deficit. The current research grant from TSA will offset a major portion of this deficit and will allow us to continue research activities in a productive fashion. Although delayed and reduced, research support from NIH has now been successfully renewed. The history of research funding for our Tourette Syndrome genetic linkage project is an excellent illustration of how support from a private foundation such as TSA can be crucial for both the initiation of a study as well as in times of budgetary crises which might jeopardize the long term success of the investigation. Roger Kurlan, M.D. University of Rochester School of Medicine, Rochester, NY Award $15,000 Tourette Association of America Inc. – Research Grant Award 1990