Evidence for an X-linked modifier gene affecting the expression of Tourette syndrome and its relevance to the increased frequency of speech, cognitive, and behavioral disorders in males.

摘要

A number of disorders affecting speech, learning, and behavior have a 3:1 or greater male:female ratio. This has usually been explained on the basis of a developmental model postulating a difference in the young male versus female brain. Tourette syndrome is a hereditary neurobehavioral disorder due to a single major autosomal gene. It is associated with learning disorders and attention deficit disorder with hyperactivity and shows a similar predilection for males. Because of the more obvious nature of the tics and vocal noises, it is uniquely suited for examining an alternative hypothesis of an X-linked modifying gene to account for the increased incidence in males. Two alternative models tested were an autosomal modifying gene and the developmental model. Family pedigrees on a series of 430 consecutive cases of Tourette syndrome with 966 age-corrected offspring were used to compare the observed affected and unaffected sons and daughters for nine different phenotype matings with the expected ratios for three different models. The X-linked modifier model provided a better fit to the observed data and accounted for marked differences in the percentage of affected sons and daughters when the father versus the mother transmitted the Tourette syndrome gene. A similar model may account for the male predominance in other genetically influenced disorders of speech, learning, and behavior.