Chromosomal Microarray Evaluated for Prenatal Diagnosis

Chromosomal microarray analysis has emerged as a primary diagnostic and has improved the detection of small genomic deletions and duplications, called copy-number variants, that are not routinely seen on karyotyping, the standard cytogenetic analysis performed.

Scientists, led by those at Columbia University Medical Center (New York, NY, USA), enrolled a total of 4,406 women undergoing prenatal diagnosis at 29 centers. Indications for prenatal diagnosis were advanced maternal age, abnormal result on Down's syndrome screening, structural anomalies on ultrasonography, and other indications. Chorionic-villus samples and some amniotic fluid specimens were sent to the central laboratory. DNA was extracted according to local protocols. Each sample was split in two with standard karyotyping performed on one portion and the other was sent to one of four laboratories for chromosomal microarray analysis.

Two array platforms were used: the first, a fourplex array designed by the investigators with reagents donated by Agilent Technologies (Santa Clara, CA, USA). The second platform was the Genome-Wide Human Single Nucleotide Polymorphism (SNP) Array 6.0 (Affymetrix, Santa Clara, CA, USA). In 98.8% of the fetal samples, microarray analysis was successful and 87.9% of samples could be used without tissue culture. Microarray analysis of the 4,282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping, but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results.

The authors concluded that for prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic data as compared with karyotyping and was equally effective in identifying aneuploidies and unbalanced rearrangements, but did not identify balanced translocations and triploidies. The study was published on December 6, 2012, in the New England Journal of Medicine.

Related Links:
Columbia University Medical Center
Agilent Technologies
Affymetrix