Experience with microarray‐based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies

Abstract

ObjectiveTo demonstrate the usefulness of microarray testing in prenatal diagnosis based on our laboratory experience.MethodsPrenatal samples received from 2004 to 2011 for a variety of indications (n = 5003) were tested using comparative genomic hybridization-based microarrays targeted to known chromosomal syndromes with later versions of the microarrays providing backbone coverage of the entire genome.ResultsThe overall detection rate of clinically significant copy number alterations (CNAs) among unbiased, nondemise cases was 5.3%. Detection rates were 6.5% and 8.2% for cases referred with abnormal ultrasounds and fetal demise, respectively. The overall rate of findings with unclear clinical significance was 4.2% but would reduce to 0.39% if only de novo CNAs were considered. In cases with known chromosomal rearrangements in the fetus or parent, 41.1% showed CNAs related to the rearrangements, whereas 1.3% showed clinically significant CNAs unrelated to the karyotype. Finally, 71% of the clinically significant CNAs found by microarray were below the resolution of conventional karyotyping of fetal chromosomes.ConclusionsMicroarray analysis has advantages over conventional cytogenetics, including the ability to more precisely characterize CNAs associated with abnormal karyotypes. Moreover, a significant proportion of cases studied by array will show a clinically significant CNA even with apparently normal karyotypes. © 2012 John Wiley & Sons, Ltd.

ACOG and SMFM guidelines for prenatal diagnosis: Is karyotyping really sufficient?

“…Our data show that at least 4.7% of patients with 1 or more fetal structural abnormalities have a clinically significant microarray abnormality that would have been missed by karyotype analysis, similar to previous reports 3, 5, 6, 7. Additionally, at least 2.5% of patients whose indication did not include a structural fetal abnormality had a CSCA detected by CMA that would have been missed by karyotyping alone.…”

Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

“…7,9,28,29 Thus our results support the hypothesis that there is a background risk of~0.5% for a clinically relevant submicroscopic chromosome abnormality (exclusive SL) in the general population. 30 In our opinion, UDs found in our cohort are of additional value in routine prenatal genomic array testing as most (4/5) of them lead to (possibly) severe (including intellectual disability and/or a reduced life expectancy) early-onset diseases, which can be missed by ultrasound examination.…”

Counseling parents before prenatal diagnosis: Do we need to say more about the sex chromosome aneuploidies?

“…No matter the level of risk, the information gained from the traditional cytogenetic or FISH analysis of chorionic villus samples or cultured fetal cells can be enhanced by DNA-array techniques, including array comparative genomic hybridization and SNP arrays that expands the detection of genetic unbalance. [Zuffardi et al, 2011;Shaffer et al, 2012]. This approach is becoming more popular due to the self-determination of women asking for PD and commercial pressure.…”