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

Gilles de la Tourette syndrome (GTS) is a common, heritable neurological disorder manifested by chronic motor and vocal tics with childhood onset. Previous 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 members with GTS or tics. Chromosome 8q22.1 was previously implicated in GTS by both association and linkage results. We therefore cloned and sequenced both translocation breakpoints from this family. The CBFA2T1 gene was identified 11 kb distal to the 8q22.1 breakpoint. Sequencing of CBFA2TI exons within 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 duplication of six nucleotides from chromosome 8 but no change in the chromosome 1 sequence. The sequences immediately flanking the breakpoints on the two chromosomes were modestly similar, but the breakpoints did not occur within known interspersed repeats. Our results add to our knowledge of the genetics of GTS and the mechanisms of balanced chromosomal translocations.