Prenatal Cytogenetic Diagnosis by Array-based copy number Analysis

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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.