BACKGROUND AND PURPOSE:

• Wang et al. (Prenatal Diagnosis, 2022) investigated the potential of genome sequencing as a single comprehensive prenatal test when fetal abnormalities are detected on ultrasound

METHODS:

• Prospective cohort study
• Participants
  • Singleton fetuses
  • Ultrasound-identified structural abnormalities | At least one finding was not a soft marker 
  • Undergoing invasive prenatal testing
• Exposures
  • Genome sequencing, in parallel with standard diagnostic testing
• Study design
  • Genetic variants were classified according to ACMG guidelines and reviewed by a panel of board-certified laboratory and clinical geneticists
• Primary outcome
  • Clinical sensitivity of genome sequencing

RESULTS:

• 37 fetuses received genome sequencing
• Routine diagnostic testing included
  • Rapid Aneuploidy Detection (RAD) by QF-PCR
  • Microarray analysis
  • DNA sequencing using gene panels or exome sequencing if indicated
• Diagnostic sequence variants identified: 14% of population (in 5 fetuses)
• Variants of uncertain significance found: 19% of population (in 7 fetuses)
• Genome sequencing also identified the 2 CNVs (5% of cases) reported by clinical microarray including

CONCLUSION:

• Genome sequencing identified all pathogenic variants reported by clinical microarray and exome sequencing
• Genome sequencing in this population achieved a diagnostic yield of 19% (5 sequence variants and 2 copy number variants)
• Variants of uncertain significance were identified in a further 19% of fetuses, which may explain structural anomalies observed
• The authors state

In conclusion, this study provides further evidence that GS has the potential to replace multiple consecutive tests, including microarray, gene panels, and ES, to provide the most comprehensive genetic analysis rapidly

Learn More – Primary Sources:

Diagnostic yield of genome sequencing for prenatal diagnosis of fetal structural anomalies

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