GENETICS OF COGNITION IN ADULT TURNER SYNDROME

描述(摘自申请者的摘要)：特纳综合征(TS)是 女性缺乏全部或部分X的人类遗传性疾病 染色体。复杂的表型包括卵巢衰竭，这是一个特征 神经认知特征和典型的身体特征。TS功能包括 不仅与完全单体X有关，而且还与部分缺失有关 短臂(XP)或长臂(XQ)(部分单体X)。受损的 视觉-空间/知觉能力是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 延误是不常见的。TS患者的神经认知功能障碍星座 很可能是多因素的，并与 遗传异常，荷尔蒙缺乏，以及其他未指明的 认知能力的决定因素。此外，还有一个额外的基因 机制，印记，可能导致与以下相关的认知缺陷 单体X。 研究人员在目前的研究中提议描绘遗传因素 这解释了成人Turner综合征的神经认知表型1) 部分单体X的TS相关神经认知表型的定位 女性，2)收集成年特纳综合征受试者的父母数据 用于印记研究，以及3)具有两种基因(X)的对比女性 染色体)和只有激素的女性的荷尔蒙异常 异常(特发性卵巢早衰)。这些研究将测试 来自初步数据的假设认知功能障碍与 单体X映射到XP的远端。 作为一种相对常见的遗传性疾病，TS具有明确的表现 为研究影响女性的遗传因素提供了机会 认知发展。有可能提供信息的遗传和表型 X基因部分缺失的TS受试者的变异。细心临床和 这些不寻常的受试者的分子特征，他们代表着 “自然界中的实验”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。特纳综合征是 这是这类表型图谱研究的优秀模型，因为它 流行率，充分表征的表型和丰富的分子 X染色体可用的资源。X缺失的表型图谱将 对遗传咨询有帮助。特定TS致病因素的特征 基因将提供对45，X，特纳综合征的病理生理学的洞察， 以及正常神经认知发展的过程。

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.