Review article| Volume 23, ISSUE 2, P457-480, June 2003

Cytogenetics and molecular cytogenetics in prenatal diagnosis

      Chromosome abnormalities account for approximately half of all spontaneous pregnancy losses, are among the most common etiologies for birth defects, and are the single most common cause of mental retardation. Since the advent of amniocentesis in the late 1960s, testing for aneuploidy has become common, especially in women of advanced maternal age and those with a positive biochemical screening test for Down syndrome. With the vast improvement in ultrasound technology to help guide invasive procedures, new prenatal diagnosis techniques have been developed that permit the analysis of numerous tissues of embryonic origin. These techniques include traditional amniocentesis, early amniocentesis (<15 weeks), transabdominal and transcervical chorionic villus sampling (CVS), fetal blood sampling, fetal skin biopsy, analysis of fetal urine, and testing of fetal cystic hygroma fluid. The laboratory evaluation of samples derived from these tissues also has expanded dramatically in the past few years. Whereas traditional cytogenetic analysis had previously been the exclusive test for chromosome abnormalities, current methodologies include fluorescence in situ hybridization (FISH) for common aneuploidies involving chromosomes 13, 18, 21, X, and Y, as well as other molecular cytogenetic tests. These molecular cytogenetic tests permit evaluation and further characterization of microdeletions, marker chromosomes, translocations, deletions, inversions, and subtelomeric deletions; and DNA-based tests can be used to rule out uniparental disomy. This review discusses the indications, techniques, and risks associated with current, clinically available prenatal diagnosis techniques and provides the laboratory perspective of how these samples can be analyzed to maximize prenatal diagnosis capability.
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