KARYOTYPE AND GENETIC ANALYSIS OF MENTAL RETARDATION

描述（改编自研究者摘要）：本研究的目的 建议是评估新的荧光原位杂交的功效 技术作为广泛性发育迟缓的辅助诊断测试 (PDD)智力迟钝（MR）。 此外，建议确定 染色体位点可能含有神经发育中重要的基因， 认知功能 假设是，筛查患有 PDD和/或MR与染色体特异性涂抹探针，端粒特异性 探针组和微缺失探针组是鉴定 PDD和MR的未知原因，并确定参与 神经发育或认知属性。 研究者的实验室 目前有能力生产一个完整的核型，包括 显带，来自使用原位荧光的信号杂交 杂交（M-FISH）和测试端粒和 使用一组端粒特异性探针， 染色体除端部着丝粒染色体的p臂外，其余染色体均为短臂。 提出要 开发用于核型分析的强大筛选方法，用于监测 端粒完整性和用于评估微缺失综合征区域 组合标记探针组。 发展这种 我们在临床细胞遗传学实验室的筛查方法， 更好的诊断和预后评估，最终， 治疗这些人。 具体地，建议筛查300名患有PDD的个体，300名患有PDD的个体， MR和大约500名正常对照受试者的染色体 使用最先进的多重杂交和成像技术 技术. 这些患者中核型畸变的相对比率 人群和正常人群核型畸变的背景率 将对个人进行评估。 新筛查的相对灵敏度 方法将与标准细胞遗传学方法进行比较。 是 预计这项建议将允许调查人员作出一项 对这些患者进行核型筛查的有效性的估计 诊断组。 此外，还将鉴定特异性探针， 将提供给其他研究人员， 易位断点位点，并应允许未来的cDNA克隆 与普遍性发育迟缓或精神发育迟缓有关， 迟钝

DESCRIPTION (Adapted from investigator's abstract): The objective of this proposal is to assess the efficacy of new fluorescence in situ hybridization techniques as adjunct diagnostic tests for pervasive developmental delay (PDD) and mental retardation (MR). In addition it is proposed to identify chromosoma loci that may harbor genes important in neural development and cognitive function. The hypothesis is that the screening of patients with PDD and/or MR with chromosome-specific painting probes, telomere-specific probe sets, and microdeletion probe sets is an effective method to identify unknown causes of PDD and MR and to identify genes involved in neurodevelopment or cognitive attributes. The investigator's laboratory currently has the capacity to produc a complete karyotype, including banding, from a signal hybridization using multicolor fluorescence in situ hybridization (M-FISH) and to test for rearrangements of telomeric and subtelomeric regions using a set of telomere-specific probes for all chromosomes except the p arms of acrocentric chromosomes. It is proposed to develop robust screening methods for karyotypic analysis, for monitoring telomere integrity and for assessing microdeletion syndrome regions using multicolor combinatorial labeled probe sets. The development of such screening methods for us in clinical cytogenetic laboratories should result in better diagnosis and prognosis assessment, and, ultimately, in better therapies for these individuals. Specifically, it is proposed to screen 300 individuals with PDD, 300 with MR, and approximately 500 normal control subjects for chromosomal abnormalities using state-of-the-art multiplex hybridization and imaging technology. The relative rates of karyotypic aberrations in these populations and the background rate of karyotypic aberrations in normal individuals will be assessed. The relative sensitivity of the new screening methods will be compared with standard cytogenetic methods. It is anticipated that this proposal will permit the investigators to make an estimate of the efficacy of karyotypic screening of patients in these diagnostic groups. In addition, specific probes will be identified that will be made available to other researchers for testing specific translocation breakpoint sites and should permit the future cloning of cDNAs that are associated with pervasive developmental delay or mental retardation.