Turner syndrome (TS) is a very common genetic disorder characterized by absence of X chromosomal material in a phenotypic female. The physical phenotypic features of TS are well-characterized, with short stature and gonadal dysgenesis being the most frequently observed. Cognitively, individuals with TS typically demonstrate normal global intellectual functioning with strengths in the verbal domain;however, many show significant deficits in visuospatial and executive functioning as well as psychosocial skills, particularly, face and emotion processing. The neural correlates of this TS cognitive-behavioral phenotype have recently begun to be explored, including neuroimaging studies of brain structure and function. However, the ability to gain meaningful insights from these studies has been limited by small sample size, large age ranges of the participants, and heterogeneity in exogenous hormone treatment status. Additionally, the impact of genetic effects such as X chromosome imprinting, on neural function and cognitive-behavioral outcome in TS, have not yet been adequately examined. Accordingly, the primary objective of this project is to use advanced, multi-modal magnetic resonance imaging (MRI) techniques, analyses of X chromosome parent-of-origin and cognitive-behavioral assessment to elucidate the effects of X monosomy and X-linked imprinting on neurodevelopment and neural function in a large cohort of young girls with TS, pre-estrogen replacement. A multi-level, cross- disciplinary approach is proposed, capitalizing on this team of investigators'expertise in behavioral neurogenetics, cognitive neuroscience, genetics and neuroimaging, as well as on the state-of the-art infrastructure available at Stanford University School of Medicine. The overarching goal of the proposed research is to generate results with implications for the design of early and more effective interventions for girls with TS in the future. In addition, these results will have broader implications for understanding genetic and epigenetic influences on brain development and organization of neural function in humans.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Freund, Lisa S
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Stanford University
Schools of Medicine
United States
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Seiler, Christof; Green, Tamar; Hong, David et al. (2018) Multi-Table Differential Correlation Analysis of Neuroanatomical and Cognitive Interactions in Turner Syndrome. Neuroinformatics 16:81-93
Green, Tamar; Saggar, Manish; Ishak, Alexandra et al. (2018) X-Chromosome Effects on Attention Networks: Insights from Imaging Resting-State Networks in Turner Syndrome. Cereb Cortex 28:3176-3183
Green, Tamar; Fierro, Kyle C; Raman, Mira M et al. (2016) Sex differences in amygdala shape: Insights from Turner syndrome. Hum Brain Mapp 37:1593-601
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Green, Tamar; Fierro, Kyle C; Raman, Mira M et al. (2016) Surface-based morphometry reveals distinct cortical thickness and surface area profiles in Williams syndrome. Am J Med Genet B Neuropsychiatr Genet 171B:402-13
Saggar, Manish; Hosseini, S M Hadi; Bruno, Jennifer L et al. (2015) Estimating individual contribution from group-based structural correlation networks. Neuroimage 120:274-84
Green, Tamar; Bade Shrestha, Sharon; Chromik, Lindsay C et al. (2015) Elucidating X chromosome influences on Attention Deficit Hyperactivity Disorder and executive function. J Psychiatr Res 68:217-25
Lepage, J-F; Hong, D S; Raman, M et al. (2014) Brain morphology in children with 47, XYY syndrome: a voxel- and surface-based morphometric study. Genes Brain Behav 13:127-34
Hong, David S; Bray, Signe; Haas, Brian W et al. (2014) Aberrant neurocognitive processing of fear in young girls with Turner syndrome. Soc Cogn Affect Neurosci 9:255-64

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