SEX OF PARENT TRANSMISSION EFFECT IN TOURETTES-SYNDROME - EVIDENCE FOR EARLIER AGE AT ONSET IN MATERNALLY TRANSMITTED CASES SUGGESTS A GENOMIC IMPRINTING EFFECT

Parent of origin effects caused by genomic imprinting may influence th e phenotypic expression of a number of heritable human disorders. To t est this phenomenon in Tourette's syndrome (TS), we studied 437 first degree relatives systematically ascertained through 57 probands. We co mpared age at onset, age at diagnosis, and phenotypic expressions as o bserved in the diagnosis of TS, chronic motor tics, and obsessive comp ulsive behavior in the offspring of affected males with the offspring of affected females. Of the 437 subjects, 16.7% had matrilineal inheri tance and 13.9% had patrilineal inheritance, as determined by family h istory methodology. Chi-square analysis of the different phenotypic ex pressions and sex of the transmitting parent failed to provide evidenc e of significant group differences. We found no significant difference s in the age at diagnosis either. However, the maternally transmitted offspring showed a significantly earlier age at onset. This points to a parent of origin effect on the putative TS gene that could be explai ned by meiotic events or even intrauterine environmental influences. T hese findings may help explain the hitherto conflicting reports about the nature of genetic transmission in TS, and suggest a need to re-exa mine family data separately for maternally and paternally transmitted cases, taking into account the possible role of imprinting.