Sex of parent transmission effect in Tourette's syndrome: evidence for earlier age at onset in maternally transmitted cases suggests a genomic imprinting effect

Abstract

Parent of origin effects caused by genomic imprinting may influence the phenotypic expression of a number of heritable human disorders. To test this phenomenon in Tourette's syndrome (TS), we studied 437 first degree relatives systematically ascertained through 57 probands. We compared age at onset, age at diagnosis, and phenotypic expressions as observed in the diagnosis of TS, chronic motor tics, and obsessive compulsive behavior in the offspring of affected males with the offspring of affected females. Of the 437 subjects, 16.7% had matrilineal inheritance and 13.9% had patrilineal inheritance, as determined by family history methodology. Chi-square analysis of the different phenotypic expressions and sex of the transmitting parent failed to provide evidence of significant group differences. We found no significant differences 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 explained by meiotic events or even intrauterine environmental influences. These findings may help explain the hitherto conflicting reports about the nature of genetic transmission in TS, and suggest a need to re-examine family data separately for maternally and paternally transmitted cases, taking into account the possible role of imprinting.