GENETICS OF COGNITION IN ADULT TURNER SYNDROME

成人特纳综合症的认知遗传学

• 批准号: 6639824
• 负责人: Judith L Ross
• 金额: $ 43.32万
• 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/6639824
• 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）：特纳综合征（TS）是 涉及缺乏全部或一部分x的女性的人类遗传疾病 染色体。复杂的表型包括卵巢衰竭，一个特征 神经认知谱和典型的物理特征。 TS功能是 不仅与完全单体X相关，还与部分删除 短（XP）或长（XQ）臂（部分单子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 延迟不常见。 TS中观察到的神经认知缺陷的星座 最有可能是多因素的，并且与 遗传异常，激素缺陷和其他未指定的 认知能力的决定因素。此外，另一种遗传 机制，印迹，可能导致与 X。 研究人员在当前研究中建议描述遗传因素 这是成人特纳综合征神经认知表型的说明1） 绘制部分单子X中与TS相关的神经认知表型 妇女，2）从成人特纳综合症受试者收集原始父母数据 用于印迹研究，以及3）与具有遗传的女性进行对比（x 染色体）和仅具有激素的女性的荷尔蒙异常 异常（特发性早产卵巢衰竭）。这些研究将测试 从初步数据中的假设，即认知功能障碍 X映射到远端XP。 作为一种相对常见的遗传疾病，具有明确的表现，TS 提出了调查影响女性的遗传因素的机会 认知发展。有可能有用的遗传和表型 具有部分X缺失的TS受试者之间的变化。仔细的临床和 这些不寻常的主题的分子表征 “自然界的实验”可以将视觉受损的TS表型联系起来 特定X染色体区域的空间/感知能力。特纳综合征是 这种表型映射研究的绝佳模型，因为它 患病率，良好的表型和分子的财富 可用于X染色体的资源。 X删除的表型映射将 有助于遗传咨询。特定TS因果关系的表征 基因将洞悉45，X，特纳综合征的病理生理学， 以及正常神经认知发展的过程。