Breakpoint sequences of an 1;8 translocation in a family with Gilles de laTourette syndrome

Gilles de la Tourette syndrome (GTS) is a common, heritable neurological di sorder manifested by chronic motor and vocal ties with childhood onset. Pre vious extensive linkage analysis failed to identify a GTS gene based on an autosomal dominant pattern of inheritance. Recently, a family was reported with a balanced chromosomal translocation t(1;8)(q21.1;q22.1) in family mem bers with GTS or ties. Chromosome 8q22.1 was previously implicated in CTS b y both association and linkage results. We therefore cloned and sequenced b oth translocation breakpoints from this family. The CBFA2T1 gene was identi fied 11 kb distal to the 8q22.1 breakpoint. Sequencing of CBFA2T1 exons wit hin 37 unrelated GTS patients failed to identify any mutations. However, it is possible that the translocation altered the expression of this gene or another nearby gene. Examination of the breakpoint sequences revealed a dup lication of six nucleotides from chromosome 8 but no change in the chromoso me 1 sequence. The sequences immediately flanking the breakpoints on the tw o chromosomes were modestly similar, but the breakpoints did not occur with in known interspersed repeats. Our results add to our knowledge of the gene tics of GTS and the mechanisms of balanced chromosomal translocations.