THE GENETIC SUSCEPTIBILITY TO GILLES-DE-LA-TOURETTE SYNDROME IN A LARGE MULTIPLE AFFECTED BRITISH KINDRED - LINKAGE ANALYSIS EXCLUDES A ROLE FOR THE GENES-CODING FOR DOPAMINE D1, D2, D3, D4, D5 RECEPTORS, DOPAMINE-BETA-HYDROXYLASE, TYROSINASE, AND TYROSINE-HYDROXYLASE

Segregation analyses have shown that Gilles de la Tourette Syndrome (GTS) is transmitted as an autosomal dominant gene disorder indicating that classical linkage analysis should be able to identify susceptibility loci. Previous studies of GTS have included investigations of neuroreceptor function, neurotransmitters, and their metabolites as well as neurotransmitter-related enzymes in an attempt to determine the pathophysiology of GTS. The neurotransmitter systems most often thought to be involved in GTS include those involving adrenaline, noradrenaline, and dopamine, We have carried out research to test the hypothesis that genes encoding proteins in the catecholamine pathways may contribute to the genetic etiology of GTS, Polymorphic markers at or near the D1, D2, D3, D4, D5 neuroreceptor gene loci as well as at the genes encoding dopamine beta hydroxylase (DBH), tyrosinase (TY) and tyrosine hydroxylase (TH) were studied in one large multiple affected pedigree. The linkage results of this investigation exclude a major role of these candidate genes in the etiology of GTS in the pedigree.