Cytogenetic microarray in structurally normal and abnormal foetuses: a five year experience elucidating increasing...

Area of Science:

• Prenatal diagnostics
• Genetics
• Reproductive medicine

Background:

• Prenatal diagnosis traditionally relies on karyotyping, which has limitations in detecting smaller chromosomal abnormalities.
• Cytogenetic microarray (CMA) offers higher resolution for identifying copy number variations and other genetic changes.
• Evaluating the diagnostic yield and clinical utility of CMA in prenatal settings is crucial.

Purpose of the Study:

• To assess the diagnostic yield of prenatal cytogenetic microarray (CMA) in both structurally normal and abnormal fetuses.
• To determine the acceptance rate of CMA for prenatal diagnosis over a five-year period.
• To compare the diagnostic performance of CMA against traditional methods.

Main Methods:

• CMA was performed on 128 fetuses (both structurally normal and abnormal).
• Quantitative fluorescence polymerase chain reaction (QF-PCR) was used to exclude aneuploidy prior to CMA.
• Foetal karyotype analysis was conducted alongside CMA.
• Variants of uncertain significance were reanalyzed.

Main Results:

• CMA detected pathogenic variants in 5.5% of all cases.
• The diagnostic yield was higher in structurally abnormal fetuses (8.8%) compared to those with high aneuploidy risk (4.7%).
• CMA identified balanced and unbalanced translocations, and low-level mosaicism.
• Reanalysis of variants of uncertain significance led to the identification of pathogenic variants.
• The acceptance rate for prenatal CMA increased five-fold over five years.

Conclusions:

• Prenatal CMA demonstrates a higher diagnostic yield in structurally abnormal fetuses.
• The study underscores the importance of integrating foetal karyotype analysis with CMA.
• Reanalysis of variants of uncertain significance is critical for maximizing diagnostic accuracy.
• The increasing acceptance rate indicates growing clinical trust in prenatal CMA.