GENETICS OF COGNITION IN ADULT TURNER SYNDROME

成人特纳综合症的认知遗传学

• 批准号: 6283547
• 负责人: Judith L Ross
• 金额: $ 43.1万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-17 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6283547
• 关键词: Turner's syndrome; behavioral /social science research tag; behavioral genetics; clinical research; cognition; female; human subject; ovary disorder; sex chromosomes; space perception; visual perception

DESCRIPTION (adapted from applicant's abstract): Turner syndrome (TS) is the human genetic disorder involving females who lack all or part of one X chromosome. The complex phenotype includes ovarian failure, a characteristic neurocognitive profile, and typical physical features. TS features are associated not only with complete monosomy X but also with partial deletions of either the short (Xp) or long (Xq) arm (partial monosomy X). Impaired visual-spatial/perceptual abilities are characteristic of TS children and adults of varying races and socioeconomic status, but global developmental delay is uncommon. The constellation of neurocognitive deficits observed in TS is most likely multifactorial and related to a complex interaction between genetic abnormalities, hormonal deficiencies, and other unspecified determinants of cognitive ability. Furthermore, an additional genetic mechanism, imprinting, may contribute to cognitive deficits associated with monosomy X. The investigators propose in the current study to delineate the genetic factors that account for the Turner syndrome neurocognitive phenotype in adults by 1) mapping the TS-associated neurocognitive phenotypes in partial monosomy X women, 2) collecting parent-of-origin data from adult Turner syndrome subjects for imprinting studies, and 3) contrasting women who have both genetic (X chromosome) and hormonal abnormalities with women who have only a hormonal abnormality (idiopathic premature ovarian failure). These studies will test the hypothesis from preliminary data that cognitive dysfunction associated with monosomy X maps to distal Xp. As a relatively common genetic disorder with well-defined manifestations, TS presents an opportunity to investigate genetic factors that influence female cognitive development. There is potentially informative genetic and phenotypic variation among TS subjects with partial X deletions. Careful clinical and molecular characterization of these unusual subjects, who represent "experiments in nature," could link the TS phenotype of impaired visual spatial/perceptual ability to specific X chromosome regions. Turner syndrome is an excellent model for such phenotype mapping studies because of its prevalence, the well-characterized phenotype, and the wealth of molecular resources available for the X chromosome. Phenotype mapping of X deletions will be helpful for genetic counseling. Characterization of specific TS causative genes would provide insight into the pathophysiology of 45,X, Turner syndrome, as well as the process of normal neurocognitive development.

描述（改编自申请人的摘要）：特纳综合症（TS）是 涉及缺乏全部或部分 X 的女性的人类遗传疾病 染色体。复杂的表型包括卵巢功能衰竭，这是一个特征 神经认知概况和典型的身体特征。 TS的特点是 不仅与 X 完全单体相关，而且与 X 的部分缺失有关 短臂 (Xp) 或长臂 (Xq)（部分单体 X）。受损 视觉空间/感知能力是 TS 儿童的特征， 不同种族和社会经济地位的成年人，但全球发展 延迟并不常见。 TS 中观察到的一系列神经认知缺陷 很可能是多因素的，并且与之间的复杂相互作用有关 遗传异常、荷尔蒙缺乏和其他未明确的 认知能力的决定因素。此外，还有一个额外的遗传 机制，印记，可能会导致与以下相关的认知缺陷： 单体X. 研究人员在当前的研究中建议描述遗传因素 解释成人特纳综合征神经认知表型 1) 绘制部分单体 X 中 TS 相关神经认知表型 女性，2) 收集成年特纳综合征受试者的原籍父母数据 用于印记研究，以及 3）对比同时具有遗传（X 染色体）和荷尔蒙异常（仅具有荷尔蒙的女性） 异常（特发性卵巢早衰）。这些研究将测试 初步数据假设认知功能障碍与 单体 X 映射到远端 Xp。 作为一种相对常见的遗传性疾病，具有明确的表现，TS 提供了研究影响女性的遗传因素的机会 认知发展。存在潜在的遗传和表型信息 具有部分 X 缺失的 TS 受试者之间的变异。细心的临床和 这些不寻常受试者的分子特征，他们代表 “自然实验”可以将视力受损的 TS 表型联系起来 对特定 X 染色体区域的空间/感知能力。特纳综合症是 此类表型作图研究的绝佳模型，因为它 患病率、明确的表型和丰富的分子 X染色体的可用资源。 X 缺失的表型作图将 对遗传咨询有帮助。特定 TS 病因的表征 基因将提供对 45,X、特纳综合征、 以及正常神经认知发展的过程。