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-IV Tourette syndrome (TS) as compared with 10 non-TS control individuals with respect to untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in each category). A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for associated comorbid conditions. This concept implies that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced amplification, duplication and recombination following chromosomal strand breakage. Further studies on a larger sample size are required to confirm the findings relating to chromosomal breakage and to analyze the possible implications for a paradigmatic shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites.
Department of Human Genetics and Developmental Biology, University of Pretoria, South Africa.
G S
GS
Gericke
I
I
Simonic
E
E
Cloete
C
C
Buckle
P J
PJ
Becker
D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D005879:Tourette Syndrome / Q000235:genetics*
D005819:Genetic Markers