INCREASED CHROMOSOMAL BREAKAGE IN TOURETTE SYNDROME PREDICTS THE POSSIBILITY OF VARIABLE MULTIPLE GENE INVOLVEMENT IN SPECTRUM PHENOTYPES -PRELIMINARY FINDINGS AND HYPOTHESIS

Increased chromosomal breakage was found in 12 patients with DSM-TV To urette syndrome (TS) as compared with 10 non-TS control individuals wi th respect to untreated, modified RPM1-, and BrdU treated lymphocyte c ultures (P < 0.001 in each category), A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associ ated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for ass ociated comorbid conditions, This concept implies that genes influenci ng higher brain functions may be situated at or near highly recombigen ic areas allowing enhanced amplification, duplication and recombinatio n following chromosomal strand breakage, Further studies on a larger s ample size are required to confirm the findings relating to chromosoma l 'breakage and to analyze the possible implications for a paradigmati c shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites. (C) 1995 Wiley-Liss, In c.