Whole genome sequencing vs chromosomal microarray analysis in prenatal diagnosis

Area of Science:

• Genetics
• Prenatal Diagnostics
• Genomic Medicine

Background:

• Whole genome sequencing (WGS) shows promise in diagnosing genetic diseases in children.
• Its application in prenatal diagnosis is less established.
• This study evaluates WGS against chromosomal microarray analysis (CMA) for routine prenatal diagnosis.

Observation:

• 185 fetuses with structural anomalies underwent parallel WGS and CMA.
• Genetic diagnoses were achieved in 15.1% of cases via WGS.
• WGS identified all CMA-detectable variants plus additional single nucleotide variations, insertions/deletions, and exonic deletions.

Findings:

• WGS detected 28 genetic diagnoses (15.1%), including 20 (10.8%) identified by CMA.
• WGS revealed 7 additional cases with single nucleotide variations/insertions/deletions and 1 with an exonic deletion.
• The incremental detection rate for WGS over CMA was 5.9%.

Implications:

• Whole genome sequencing demonstrates superior accuracy and efficacy for prenatal diagnosis of fetal structural anomalies.
• It identifies a wider spectrum of genetic variants than CMA, including single nucleotide variations and repeat expansions.
• WGS shows potential as a valuable, comprehensive prenatal diagnostic tool with acceptable turnaround times.