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: 8133017
• 负责人: RONALD WAPNER
• 金额: $ 50.51万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-08 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8133017
• 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; Institutional Review Boards; 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; 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，而无需进行足够的研究。在产前诊断的领域中，比较基因组杂交微阵列（ACGH）方法的需求尤为重要，有可能显着改善检测到的临床意义异常的范围，并且有可能在基因组中揭示临床上不重要的基因组变化，如果无法进行适当评估，则可能导致不正确的诊断。因此，我们提出了一项研究，以比较ACGH在常规产前诊断实践中与常规细胞遗传学的准确性和功效。将从大量产前诊断人群中招募两名患者（约4,000名）。这将包括一系列1750名接受侵入性测试的常规适应症的患者，并将在这两种技术的常规实践中提供有关鉴定标准肾上腺素的常规实践和发现其他细胞遗传学发现的信息。第二个人群将包括2250例超声鉴定的胎儿结构异常，旨在探讨ACGH发现的细胞遗传学异常的潜在范围和临床意义。所有患者将获得IRB批准的方法的同意，并将获得常规的诊断结果以及已知临床意义的ACGH发现。计划进行两年的随访，以评估未知临床意义的ACGH发现的临床相关性。所有同意患者的样本和相关数据将用于评估新兴技术或基因组水平探索特定畸形的病因。实验室程序将在所有实验室中进行验证，以确保实验室间的绩效，并在初始病例的初始部分进行确定适当的组织样本以确定适当的组织样本。所有诊断结果将以标准的临床格式处理，所有研究数据将通过所有数据传输到数据协调中心进行持有和分析。为患者招募和实验室加工分配了大约2。5年；在选定病例和数据处理中，妊娠结局和婴儿随访的额外还有2。5年。