Prenatal Cytogenetic Diagnosis by Array-based copy number Analysis

描述(申请人提供)：在没有充分研究的情况下，微阵列技术正迅速从实验室过渡到临床诊断实践。评估的必要性在产前诊断领域尤为重要，在产前诊断领域，比较基因组杂交微阵列(ACGH)方法有可能显著改善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，如果评估不当，可能会导致错误诊断。因此，我们建议进行一项研究，比较aCGH和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。将从一个庞大的产前诊断人群中招募两组患者(约4000人)。这将包括1750名接受常规适应症侵入性测试的患者的序列，并将提供关于这两种技术在识别标准非整倍体和发现额外细胞遗传学发现方面在常规实践中的比较表现的信息。第二个群体将包括2250例超声识别出胎儿结构异常的孕妇，旨在探索aCGH发现的微小细胞遗传学异常的潜在范围和临床意义。所有患者都将得到IRB批准的方法的同意，并将获得常规诊断结果和已知临床意义的CGH结果。计划进行两年的随访，以评估未知临床意义的aCGH结果的临床相关性。所有同意的患者的样本和相关数据将被储存起来，用于未来对新兴技术的评估，或用于特定畸形病因的基因组水平探索。将在所有实验室中验证实验室程序，以确保实验室间的性能，并将在最初的病例中运行确定用于诊断的适当组织样本的重复程序。所有诊断结果将以标准的临床格式处理，所有研究数据将被盲目分析，所有数据将传输到数据协调中心进行保存和分析。为患者招募和实验室处理分配了大约2.5年；在选定的案例中为妊娠结局和婴儿随访以及数据处理另外分配了2.5年。

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.