Prenatal Cytogenetic Diagnosis by Array-based copy number Analysis

基于阵列的拷贝数分析进行产前细胞遗传学诊断

• 批准号: 7935128
• 负责人: RONALD WAPNER
• 金额: $ 74.5万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7935128
• 关键词: Aneuploidy; Anxiety; Area; Chromosome abnormality; Clinical; Consent; Cytogenetic Analysis; Cytogenetics; Data; Data Coordinating Center; Databases; Detection; Development; Devices; Diagnosis; Diagnostic; Emerging Technologies; Etiology; Evaluation; Future; Genetic Polymorphism; Genome; Growth Disorders; Infant; International; Laboratories; Laboratory Procedures; Logistics; Methods; Microarray Analysis; Microscopy; Oligonucleotides; Online Systems; Patau' s syndrome; Patient Recruitments; Patients; Performance; Pilot Projects; Population; Prader-Willi Syndrome; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis; Procedures; Process; Provider; Recruitment Activity; Research; Research Ethics Committees; Resolution; Resource Sharing; Resources; Running; Sampling; Series; Technology; Testing; Time; Tissue Sample; Tissues; Ultrasonography; base; clinically relevant; clinically significant; comparative; comparative genomic hybridization; computerized data processing; cost; cost effectiveness; fetal; follow-up; improved; malformation; new technology; patient population; prenatal; repository; routine practice; sample collection; sex; tool

DESCRIPTION (provided by applicant): Microarray technology is rapidly transitioning from the laboratory to clinical diagnostic practice without adequate study. The need for evaluation is particularly important in the area of prenatal diagnosis where comparative genomic hybridization microarray (aCGH) approaches have the potential to significantly improve the range of clinically significant anomalies detected but also has the potential for revealing clinically unimportant changes in the genome that, if not appropriately evaluated, could result in incorrect diagnosis. Accordingly, we propose a study comparing the accuracy and efficacy of aCGH to conventional cytogenetics in routine prenatal diagnostic practice. Two populations of patients (approximately 4,000) will be recruited from a large prenatal diagnostic population. This will include a sequential series of 1750 patients undergoing invasive testing for routine indications and will yield information on the comparative performance in routine practice of the two technologies in identifying standard aneuploidy and in uncovering additional cytogenetic findings. The second population will include 2250 pregnancies with ultrasound identified fetal structural anomalies and is intended to explore the potential range and clinical significance of subtle cytogenetic abnormalities found by aCGH. All patients will be consented by IRB approved methods and will receive routine diagnostic results as well as aCGH findings of known clinical significance. A two year follow-up is planned to evaluate the clinical relevance of aCGH findings of unknown clinical significance. Samples and pertinent data from all consenting patients will be banked for future use in the evaluation of emerging technologies or for the genome level exploration of the etiology of specific malformations. Laboratory procedures will be validated in all labs to assure inter-laboratory performance, and duplicate procedures to determine the appropriate tissue sample for diagnostic use will be run on an initial portion of cases. All diagnostic results will be handled in a standard clinical format and all research data will be analyzed blindly with all data transmitted to a Data Coordinating Center for holding and analysis. Approximately 2.5 years are allotted for patient recruitment and laboratory processing; with an additional 2.5 years for pregnancy outcome and infant follow-up in selected cases, as well as data processing.

描述（由申请人提供）：微阵列技术正在迅速从实验室过渡到临床诊断实践，没有充分的研究。在产前诊断领域，评估的需求尤为重要，因为比较基因组杂交微阵列（aCGH）方法有可能显著提高检测到的临床显著异常的范围，但也有可能揭示基因组中临床上不重要的变化，如果不适当评估，可能导致错误的诊断。因此，我们建议进行一项研究，比较aCGH与常规细胞遗传学在常规产前诊断实践中的准确性和有效性。将从大量产前诊断人群中招募两组患者（约4,000人）。这将包括对1750例患者进行常规适应症的侵入性检测，并将在常规实践中获得两种技术在识别标准非整倍体和发现其他细胞遗传学发现方面的比较表现的信息。第二组将包括2250例超声发现胎儿结构异常的孕妇，旨在探讨aCGH发现的细微细胞遗传学异常的潜在范围和临床意义。所有患者将通过IRB批准的方法同意，并将获得常规诊断结果以及已知临床意义的aCGH结果。计划进行为期两年的随访，以评估未知临床意义的aCGH发现的临床相关性。来自所有同意患者的样本和相关数据将被储存起来，用于未来新兴技术的评估或特定畸形病因的基因组水平探索。将在所有实验室验证实验室程序，以确保实验室间的表现，并将在最初部分病例中运行重复程序，以确定用于诊断的适当组织样本。所有诊断结果将以标准临床格式处理，所有研究数据将进行盲目分析，所有数据将传输到数据协调中心保存和分析。大约有2.5年的时间用于患者招募和实验室处理；另外还有2.5年的妊娠结局和选定病例的婴儿随访，以及数据处理。