We have characterized a highly unusual two-generation pedigree in which Tourette's syndrome is segregated in an autosomal dominant fashion. Given that Tourette's syndrome has a population prevalence of 1% and a rate of recurrence of 10 to 15% among first-degree relatives of an affected person, it is extremely unlikely that all eight offspring of an affected parent would have Tourette's syndrome by chance, suggesting that this kindred indeed carries a mendelian form of the syndrome. The finding of a single segment of the genome that is shared among all affected members with a clearly deleterious mutation within this interval is also highly unlikely to occur by chance alone. Though the accepted standard for statistical significance on the basis of parametric linkage of a mendelian trait is a lod score of 3.0, these findings strongly point to a causal relationship between the identified mutation and Tourette's syndrome in this family.
