RETT SYNDROME GENETICS, PATHOGENESIS & SEARCH FOR MARKER

RETT 综合征遗传学、发病机制

• 批准号: 7420414
• 负责人: SAKKUBAI R NAIDU
• 金额: $ 3.74万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420414
• 关键词: Rett syndrome; children

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The general goal of the Rett Syndrome program project is to improve the understanding of the genetics and pathogenesis of Rett syndrome, as a first step to improved diagnosis and treatment. A significant component of this collaboration is MR neuroimaging and MR spectroscopic imaging. There are several aspects to this research for which collaboration with the resource is extremely important. First of all, a large fraction of the subjects with Rett Syndrome are children, who require a special environment to feel comfortable to participate in the scanning. Also, many adults with Rett syndrome have mental retardation and need special attention in order to be scanned successfully. The magnets in our center have the shortest bore available of all whole-body 1.5T and 3T scanners. The bore is accessible from the back and the front and allows the subject to keep eye contact with its care giver. This child-friendly environment for MR imaging is expected to drastically reduce the requir ements for sedation because the child is more at ease. The Kirby Center also contains a mock scanner in which the children or other subjects can be trained to hold still and perform tasks in the magnet. Together with the child psychologists at Kennedy Krieger, Dr. Naidu and the Center staff will work on optimizing the imaging of children. The latter is important because it is expected that functional testing of these children can provide much needed information on their behavior in a quantitative reproducible manner. The Rett Syndrome research program relates to all of the development projects proposed in this resource application. The design of flow and oxygenation methods and techniques for improved image registration and processing in Project 1 will be used to examine the hypothesis of abnormal blood flow and oxygen metabolism in the frontal lobe in Rett syndrome (see below). The spectroscopy tools in project 2 will be used to determine levels of neurotransmitters and other brain chemicals with respect to normal children. Project 3 will, for the first time, provide the possibility to compare the wiring in the brains of children with Rett syndrome to that of normal children. Projects 4 will be crucial in establishing shapes of brain regions and in combining the results of all projects in general maps that will be assessed as a function of developmental stage.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Rett综合征项目的总体目标是提高对Rett综合征遗传学和发病机制的理解，作为改善诊断和治疗的第一步。这项合作的一个重要组成部分是MR神经成像和MR光谱成像。这项研究有几个方面与资源的合作是极其重要的。首先，患有Rett综合征的受试者中有很大一部分是儿童，他们需要一个特殊的环境来舒适地参与扫描。此外，许多患有Rett综合征的成年人患有智力迟钝，需要特别注意才能成功扫描。我们中心的磁体具有所有全身1.5T和3 T扫描仪中最短的孔径。该孔可从后面和前面进入，并允许受试者与其护理人员保持目光接触。这种儿童友好的MR成像环境预计将大大减少镇静的要求，因为孩子更放心。柯比中心还包含一个模拟扫描仪，儿童或其他受试者可以在其中接受训练，以保持静止并在磁铁中执行任务。Naidu博士和该中心的工作人员将与Kennedy Krieger的儿童心理学家一起致力于优化儿童成像。后者是重要的，因为它是预期的功能测试，这些儿童可以提供急需的信息，他们的行为在一个定量的可重复的方式。Rett综合征研究计划涉及本资源申请中提出的所有开发项目。项目1中用于改进图像配准和处理的血流和氧合方法和技术的设计将用于检查Rett综合征额叶血流和氧代谢异常的假设（见下文）。项目2中的光谱学工具将用于确定正常儿童的神经递质和其他大脑化学物质的水平。项目3将首次提供将Rett综合征儿童的大脑布线与正常儿童进行比较的可能性。项目4对于确定大脑区域的形状以及将所有项目的结果结合到通用地图中至关重要，该地图将根据发育阶段进行评估。