The parent-of-origin of the extra X chromosome may differentially affect psychopathology in klinefelter syndrome

Hilgo Bruining, Sophie Van Rijn, Hanna Swaab, Jacques Giltay, Wendy Kates, Martien J.H. Kas, Herman Van Engeland, Leo De Sonneville

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Background Several genetic mechanisms have been proposed for the variability of the Klinefelter syndrome (KS) phenotype such as the parent-of-origin of the extra X chromosome. Parent-of-origin effects on behavior in KS can possibly provide insights into X-linked imprinting effects on psychopathology that may be extrapolated to other populations. Here, we investigated whether the parent-of-origin of the supernumerary X chromosome influences autistic and schizotypal symptom profiles in KS. Methods Parent-of-origin of the X chromosome was determined through analysis of the polymorphic CAG tandem repeat of the androgen receptor gene. Autistic traits (Autism Diagnostic InterviewRevised) were measured in a younger KS sample (n = 33) with KS and schizotypal traits (Schizotypal Personality Questionnaire) were assessed in an older KS sample (n = 43). Scale scores on these questionnaires were entered in statistical analyses to test parent-of-origin effects. Results The results show that parent-of-origin of the X chromosome is reflected in autistic and schizotypal symptomatology. Differences were shown in the degree of both schizotypal and autistic symptoms between the parent-of-origin groups. Furthermore, the parent-of-origin could be correctly discriminated in more than 90% of subjects through Autism Diagnostic Interview-Revised scales and in around 80% of subjects through Schizotypal Personality Questionnaire scales. Conclusions These findings point to parent-of-origin effects on psychopathology in KS and indicate that imprinted X chromosomal genes may have differential effects on autistic and schizotypal traits. Further exploration of imprinting effects on psychopathology in KS is needed to confirm and expand on our findings.

Original languageEnglish
Pages (from-to)1156-1162
Number of pages7
JournalBiological Psychiatry
Issue number12
Publication statusPublished - 15 Dec 2010


  • Aneuploidy
  • Klinefelter
  • autism
  • genetics
  • genomic conflict
  • imprinting
  • parent-of-origin
  • schizophrenia
  • schizotypy
  • sex chromosomal disorder
  • sexual difference

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