TOURETTE-SYNDROME IN A PEDIGREE WITH A 7-18-TRANSLOCATION - IDENTIFICATION OF A YAC SPANNING THE TRANSLOCATION BREAKPOINT AT 18Q22.3

Tourette syndrome is a neuropsychiatric disorder characterized by the presence of multiple, involuntary motor and vocal tics. Associated pat hologies include attention deficit disorder and obsessive-compulsive d isorder (OCD), Extensive linkage analysis based on an autosomal domina nt mode of transmission with reduced penetrance has failed to show lin kage with polymorphic markers, suggesting either locus heterogeneity o r a polygenic origin for Tourette syndrome. An individual diagnosed wi th Tourette syndrome has been described carrying a constitutional (7;1 8) chromosome translocation (Comings et al. 1986). Other family member s carrying the translocation exhibit features seen in Tourette syndrom e including motor tics, vocal tics, and OCD. Since the disruption of s pecific genes by a chromosomal rearrangement can elicit a particular p henotype, we have undertaken the physical mapping of the 7;18 transloc ation such that genes mapping at the site of the breakpoint can be ide ntified and evaluated for a possible involvement in Tourette syndrome. Using somatic cell hybrids retaining either the der(7) or the der(18) , a more precise localization of the breakpoints on chromosomes 7 and 18 have been determined. Furthermore, physical mapping has identified two YAC clones that span the translocation breakpoint on chromosome 18 as determined by FISH. These YAC clones will be useful for the eventu al identification of genes that map to chromosomes 7 and 18 at the sit e of the translocation.