The following is a summary of “Whole genome sequencing vs chromosomal microarray analysis in prenatal diagnosis,” published in the SEPTEMBER 2023 issue of Obstetrics and Gynecology by Hu, et al.

Recent studies have suggested that whole genome sequencing offers greater diagnostic yield for identifying genomic variants than chromosomal microarray analysis for infants and children with suspected genetic diseases. However, the use and evaluation of whole genome sequencing for prenatal diagnosis is still limited. For a study, researchers sought to assess the accuracy, effectiveness, and additional diagnostic value of whole genome sequencing compared to chromosomal microarray analysis for routine prenatal diagnosis.

The prospective study enrolled 185 unselected singleton fetuses with ultrasound-detected structural anomalies. Each sample underwent both whole genome sequencing and chromosomal microarray analysis in parallel. Aneuploidies and copy number variations were detected and analyzed in a blinded fashion. Single nucleotide variations, insertions, and deletions were confirmed through Sanger sequencing, and trinucleotide repeat expansion variants were verified using polymerase chain reaction with fragment-length analysis.

Whole genome sequencing provided genetic diagnoses for 28 (15.1%) cases. In the 20 (10.8%) diagnosed cases found by chromosomal microarray analysis, whole genome sequencing not only found all of these aneuploidies and copy number variations but also found 1 case with an exonic deletion of COL4A2 and 7 (3.8%) cases with single nucleotide variations or insertions and deletions. Additionally, 3 incidental findings were discovered, including the expansion of the trinucleotide repeat in ATXN3, a splice-site variant in ATRX, and an ANXA11 missense mutation in a case of trisomy 21.

In comparison to chromosomal microarray analysis, whole genome sequencing increased the additional detection rate by 5.9% (11/185). Whole genome sequencing not only detected aneuploidies and copy number variations but also identified single nucleotide variations, insertions and deletions, trinucleotide repeat expansions, and exonic copy number variations with high accuracy and within an acceptable turnaround time (3–4 weeks). These results suggest that whole genome sequencing has the potential to become a promising prenatal diagnostic test for fetuses with structural anomalies.

Source: ajog.org/article/S0002-9378(23)00149-7/fulltext