The Burner syndrome-associated neurocognitive phenotype maps to distal Xp

Turner syndrome (TS) is associated with a characteristic neurocognitive pro file that includes impaired visuospatial/perceptual abilities. We used a mo lecular approach to identify a critical region of the X chromosome for neur ocognitive 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 phe notype. Only subjects missing similar to 10 Mb of distal Xp manifested the specified neurocognitive profile. The phenotype was seen with either patern ally or maternally inherited deletions and with either complete or incomple te skewing of X inactivation. Fine mapping of informative deletions implica ted a critical region of <2 Mb within the pseudoautosomal region (PAR1). We conclude that haploinsufficiency of PAR1 gene(s) is the basis for suscepti bility to the TS neurocognitive phenotype.