Abstract
ObjectiveTo evaluate the effectiveness of whole-genome array comparative genomic hybridization (aCGH) in prenatal diagnosis in Hong Kong.MethodsArray CGH was performed on 220 samples recruited prospectively as the first-tier test study. In addition 150 prenatal samples with abnormal fetal ultrasound findings found to have normal karyotypes were analyzed as a ‘further-test’ study using NimbleGen CGX-135K oligonucleotide arrays.ResultsArray CGH findings were concordant with conventional cytogenetic results with the exception of one case of triploidy. It was found in the first-tier test study that aCGH detected 20% (44/220) clinically significant copy number variants (CNV), of which 21 were common aneuploidies and 23 had other chromosomal imbalances. There were 3.2% (7/220) samples with CNVs detected by aCGH but not by conventional cytogenetics. In the ‘further-test’ study, the additional diagnostic yield of detecting chromosome imbalance was 6% (9/150). The overall detection for CNVs of unclear clinical significance was 2.7% (10/370) with 0.9% found to be de novo. Eleven loci of common CNVs were found in the local population.ConclusionWhole-genome aCGH offered a higher resolution diagnostic capacity than conventional karyotyping for prenatal diagnosis either as a first-tier test or as a ‘further-test’ for pregnancies with fetal ultrasound anomalies. We propose replacing conventional cytogenetics with aCGH for all pregnancies undergoing invasive diagnostic procedures after excluding common aneuploidies and triploidies by quantitative fluorescent PCR. Conventional cytogenetics can be reserved for visualization of clinically significant CNVs.
Highlights
Conventional cytogenetics has been the gold standard for detecting chromosomal abnormalities in prenatal diagnosis
Parental blood samples were obtained at the time of consent in case information on inheritance of copy number variants (CNV) is necessary for further interpretation of prenatal results
In addition to the evaluation study, abnormal findings of 12 prenatal samples tested by conventional cytogenetics and requiring characterization were assessed using array comparative genomic hybridization (aCGH)
Summary
Conventional cytogenetics has been the gold standard for detecting chromosomal abnormalities in prenatal diagnosis It enables the examination of genome-wide numerical and structural abnormalities at microscopic level, and can achieve a resolution of 5–10 Mb [1]. Various molecular cytogenetic techniques, such as Quantitative Fluorescent Polymerase Chain Reaction (QF-PCR) [2,3] and Fluorescent In Situ Hybridization (FISH) technology, could complement the detection of chromosomal abnormalities and offer faster turn-around times. These methods are targeted to detect specific chromosomal abnormalities and are dependent on the chromosomal probe used. Whole-genome array comparative hybridization (aCGH) provides high resolution detection of genomic alterations, and allows refinement of breakpoints on chromosome rearrangements
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