Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function

Abstract

Turner's syndrome is a sporadic disorder of human females in which all or part of one X chromosome is deleted¹. Intelligence is usually normal² but social adjustment problems are common³. Here we report a study of 80 females with Turner's syndrome and a single X chromosome, in 55 of which the X was maternally derived (45,X^m) and in 25 it was of paternal origin (45,X^p). Members of the 45,X^p group were significantly better adjusted, with superior verbal and higher-order executive function skills, which mediate social interactions⁴. Our observations suggest that there is a genetic locus for social cognition, which is imprinted⁵ and is not expressed from the maternally derived X chromosome. Neuropsychological and molecular investigations of eight females with partial deletions of the short arm of the X chromosome⁶ indicate that the putative imprinted locus escapes X-inactivation⁷, and probably lies on Xq or close to the centromere on Xp. If expressed only from the X chromosome of paternal origin, the existence of this locus could explain why 46,XY males (whose single X chromosome is maternal) are more vulnerable to developmental disorders of language and social cognition, such as autism, than are 46,XX females⁸.