Brain Structure and Cognition in Cystinosis

描述（由申请人提供）：在过去的十年中，人们越来越关注遗传对行为和认知的影响。对这种遗传条件的研究为我们提供了一个独特的机会，在一个遗传定义明确的人群中研究基因-行为和大脑-行为的关系。肾病性胱氨酸病是一种遗传性疾病，其中已记录了视觉空间功能障碍的特定认知特征，具有保留的视觉感知功能、智力和语言。脑MRI扫描和神经病理学数据表明白色物质的髓鞘形成可能存在缺陷。这些问题背后的机制，以及随着时间的推移功能障碍的过程尚不清楚。拟定研究将采用纵向方法研究胱氨酸病儿童和青少年以及对照组随时间推移的视知觉和视觉空间功能;对胱氨酸病儿童和青少年进行系列MR/扫描;并对MRI扫描进行形态学分析，以确定胱氨酸病和对照组大脑之间的区域结构差异，特别是在白色物质中。该研究将利用该实验室获得的胱氨酸病人群中已经存在的大型认知研究数据库，以便之前测试的受试者将接受重复测试，以提供有关儿童年龄增长时认知功能和大脑结构变化的纵向信息。这项研究的结果提供了了解早期代谢和遗传功能障碍对随后的大脑发育，结构和功能的作用，并确定是否存在的代谢紊乱可以产生对大脑功能的渐进性有害影响的潜力。研究结果还可能为开发早期干预措施提供基础，这些干预措施针对因遗传疾病而存在认知缺陷的儿童。

DESCRIPTION (provided by applicant): There has been increasing interest in the role of genetic influences on behavior and cognition in the last decade. Studies of such genetic conditions provide us with a unique opportunity to study gene-behavior and brain-behavior relationships in a genetically well-defined population. Nephropathic cystinosis is a genetic disorder in which a specific cognitive profile of visual spatial dysfunction, with spared visual perceptual function, intelligence, and language, has been documented. Brain MRI scans and neuropathological data have suggested a possible defect in myelination of the white matter. The mechanisms underlying these problems, and the course of the dysfunction over time are not known. The proposed study will use a longitudinal approach to study visual perceptual and visual spatial function over time in children and adolescents with cystinosis as well as controls; to perform serial MR/scans on children and adolescents with cystinosis; and to conduct morphometric analyses of the MRI scans to identify regional structural differences between cystinosis and control brains, in particular in the white matter. The study will take advantage of the already existent large database of cognitive studies in the cystinosis population obtained by this laboratory, so that subjects previously tested will undergo repeat testing to provide longitudinal information about changes in cognitive function and brain structure as the child gets older. The results of this study provide the potential for understanding the role of early metabolic and genetic dysfunction on subsequent brain development, both structural and functional, and for determining whether the presence of the metabolic disorder can produce a progressive deleterious effect on brain function. The study results may also provide a basis for developing early interventions for children "at risk" for cognitive deficits because of the presence of a genetic disorder.