Increased expression of aphidicolin-induced common fragile sites in Tourette syndrome: the key to understand the genetics of comorbid phenotypes?

In a comparison of 80 common aphidicolin-induced fragile sites (FS) between 26 DSM-IV Tourette syndrome (TS) and 24 control individuals, the mean of the summed break frequencies following mild aphidicolin pretreatment was significantly higher in TS individuals than in controls (P < 0.001). Other breakpoints encountered during this study, i.e., random breaks, breaks corresponding to rare FS, and breakpoints recorded by others but not listed as common FS according to the Chromosome Coordinating Meeting [1992] were listed as category II breakpoints. By using the most significantly different mean FS breakage figures between TS and control individuals, further stepwise discriminant analysis allowed identification of TS individuals from only a few sites in both the common FS and category II breakpoint groups. Future research needs to focus on confirmation of altered common fragile site expression in association with behavioral variation, whether expression of certain discriminatory sites concurs with specific comorbid disorder expression; the nature of the molecular alterations at these FS and the implications of a genomic instability phenotype for the mapping of a primary TS gene or genes.