Brain Structure and Cognition in Cystinosis

描述(由申请人提供)：在过去的十年里，人们对遗传影响对行为和认知的作用越来越感兴趣。对这种遗传病的研究为我们提供了一个独特的机会来研究基因-行为和大脑-行为关系，在一个基因定义明确的人群中。肾性胱氨酸病是一种遗传性疾病，在这种疾病中，视觉空间功能障碍的特定认知特征已经被记录在案，但视觉感知功能、智力和语言都没有记录。脑部核磁共振扫描和神经病理数据表明，白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。这项拟议的研究将使用纵向方法来研究患有半胱氨酸病的儿童和青少年以及对照组随时间的视觉感知和视觉空间功能；对患有半胱氨酸病的儿童和青少年进行系列MR/扫描；并对MRI扫描进行形态计量分析，以确定半胱氨酸病和对照组大脑之间的区域结构差异，特别是在脑白质方面。这项研究将利用该实验室获得的已有的针对胱氨酸病人群的认知研究大型数据库，以便之前接受测试的受试者将接受重复测试，以提供有关儿童随着年龄增长认知功能和大脑结构变化的纵向信息。这项研究的结果为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)的作用提供了潜在的可能性，并为确定代谢障碍的存在是否会对大脑功能产生渐进的有害影响提供了可能性。这项研究结果也可能为为因存在遗传障碍而出现认知缺陷的“高危”儿童制定早期干预措施提供基础。

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.