Gene, Brain and Behavior in Turner Syndrome

特纳综合症的基因、大脑和行为

• 批准号: 7037001
• 负责人: Allan L Reiss
• 金额: $ 46.52万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037001
• 关键词: Turner' s syndrome; behavioral /social science research tag; behavioral genetics; bioimaging /biomedical imaging; brain mapping; brain morphology; clinical research; cognition; developmental neurobiology; epigenetics; executive function; family genetics; female; functional magnetic resonance imaging; human subject; middle childhood (6-11); neural information processing; neuroimaging; neuropsychology; sex linked trait

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：特纳综合征（TS）是一种非常常见的遗传疾病，其特征是表型女性中缺乏X染色体材料。 TS的物理表型特征经过良好的特征，其身材矮小，性腺失调症是最常观察到的。在认知上，具有TS的个体通常表现出正常的全球智力功能，并在言语领域中具有优势。但是，许多人在视觉空间和执行功能以及社会心理技能，尤其是面部和情感处理方面表现出严重的缺陷。该TS认知行为表型的神经相关性最近开始探索，包括对脑结构和功能的神经影像学研究。但是，从这些研究中获得有意义的见解的能力受到样本量，参与者的年龄范围和外源激素治疗状况的异质性的限制。此外，尚未充分检查遗传作用，例如X染色体印记，对TS中神经功能和认知行为结果的影响。 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.提出了一种多层次的跨学科方法，利用了该研究人员在行为神经源性，认知神经科学，遗传学和神经影像学以及斯坦福大学医学院可用的最新基础设施方面的专业知识。拟议的研究的总体目标是产生结果，对未来TS女孩的早期和更有效的干预措施的设计产生影响。此外，这些结果将对了解人类对脑发育和神经功能的组织的遗传和表观遗传影响具有更广泛的影响。