The Turner syndrome-associated neurocognitive phenotype maps to distal Xp

Am J Hum Genet. 2000 Sep;67(3):672-81. doi: 10.1086/303039. Epub 2000 Aug 8.

Abstract

Turner syndrome (TS) is associated with a characteristic neurocognitive profile that includes impaired visuospatial/perceptual abilities. We used a molecular approach to identify a critical region of the X chromosome for neurocognitive aspects of TS. Partial deletions of Xp in 34 females were mapped by FISH or by loss of heterozygosity of polymorphic markers. Discriminant function analysis optimally identified the TS-associated neurocognitive phenotype. Only subjects missing approximately 10 Mb of distal Xp manifested the specified neurocognitive profile. The phenotype was seen with either paternally or maternally inherited deletions and with either complete or incomplete skewing of X inactivation. Fine mapping of informative deletions implicated a critical region of <2 Mb within the pseudoautosomal region (PAR1). We conclude that haploinsufficiency of PAR1 gene(s) is the basis for susceptibility to the TS neurocognitive phenotype.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Body Height / genetics
  • Child
  • Chromosome Breakage / genetics
  • Chromosome Deletion
  • Chromosome Mapping
  • Dosage Compensation, Genetic
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Middle Aged
  • Mosaicism / genetics*
  • Ovary / physiopathology
  • Phenotype
  • Space Perception / physiology*
  • Turner Syndrome / genetics*
  • Turner Syndrome / physiopathology*
  • Visual Perception / genetics*
  • Visual Perception / physiology
  • X Chromosome / genetics*