title: Effects of sex chromosome dosage on corpus callosum morphology in supernumerary sex chromosome aneuploidies.
abstract: BACKGROUND
  Supernumerary sex chromosome aneuploidies (sSCA) are characterized by the presence of one or more additional sex chromosomes in an individual's karyotype; they affect around 1 in 400 individuals. Although there is high variability, each sSCA subtype has a characteristic set of cognitive and physical phenotypes. Here, we investigated the differences in the morphometry of the human corpus callosum (CC) between sex-matched controls 46,XY (N =99), 46,XX (N =93), and six unique sSCA karyotypes: 47,XYY (N =29), 47,XXY (N =58), 48,XXYY (N =20), 47,XXX (N =30), 48,XXXY (N =5), and 49,XXXXY (N =6).
  
  
  METHODS
  We investigated CC morphometry using local and global area, local curvature of the CC boundary, and between-landmark distance analysis (BLDA). We hypothesized that CC morphometry would vary differentially along a proposed spectrum of Y:X chromosome ratio with supernumerary Y karyotypes having the largest CC areas and supernumerary X karyotypes having significantly smaller CC areas. To investigate this, we defined an sSCA spectrum based on a descending Y:X karyotype ratio: 47,XYY, 46,XY, 48,XXYY, 47,XXY, 48,XXXY, 49,XXXXY, 46,XX, 47,XXX. We similarly explored the effects of both X and Y chromosome numbers within sex. Results of shape-based metrics were analyzed using permutation tests consisting of 5,000 iterations.
  
  
  RESULTS
  Several subregional areas, local curvature, and BLDs differed between groups. Moderate associations were found between area and curvature in relation to the spectrum and X and Y chromosome counts. BLD was strongly associated with X chromosome count in both male and female groups.
  
  
  CONCLUSIONS
  Our results suggest that X- and Y-linked genes have differential effects on CC morphometry. To our knowledge, this is the first study to compare CC morphometry across these extremely rare groups.
authors.affiliation: Imaging Genetics Center, Institute for Neuro Imaging and Informatics, USC, 4676 Admiralty Way, Marina del Rey, Los Angeles 90292, CA, USA.
authors.forename: Benjamin S C
authors.initials: BS
authors.lastname: Wade
authors.affiliation: Department of Neurology, Ahmanson-Lovelace Brain Mapping Center, UCLA, Los Angeles 90095, CA, USA.
authors.forename: Shantanu H
authors.initials: SH
authors.lastname: Joshi
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown 02129, MA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda 20892-1600, MD, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Blumenthal
authors.affiliation: Institute for Neuro Imaging and Informatics, Keck School of Medicine, USC, Los Angeles 90032, CA, USA.
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.affiliation: Imaging Genetics Center, Institute for Neuro Imaging and Informatics, USC, 4676 Admiralty Way, Marina del Rey, Los Angeles 90292, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda 20892-1600, MD, USA.
authors.forename: Jay N
authors.initials: JN
authors.lastname: Giedd
keywords: Aneuploidies; Corpus callosum; Sex chromosomes; Sexual differentiation; Statistical shape analysis