Application of chromosome microarray analysis in prenatal diagnosis

Area of Science:

• Genetics
• Prenatal Diagnosis
• Molecular Cytogenetics

Background:

• Prenatal diagnosis relies on accurate detection of fetal chromosomal abnormalities.
• Traditional karyotype analysis has limitations in detecting certain genetic variations.
• Chromosomal Microarray Analysis (CMA) offers a higher resolution approach.

Purpose of the Study:

• To evaluate the clinical utility of CMA in prenatal diagnosis.
• To compare CMA with karyotype analysis in identifying fetal genetic abnormalities.
• To assess the diagnostic yield of CMA across different ultrasound findings.

Main Methods:

• Analyzed 477 amniocentesis cases comparing chromosome karyotype and CMA results.
• Stratified analysis based on the presence and type of ultrasound abnormalities.
• Compared detection rates of chromosomal abnormalities, pathogenic copy number variations (pCNVs), and variants of unknown significance (VOUS).

Main Results:

• CMA identified 15.88% of chromosomal abnormalities, including aneuploidies, rearrangements, and chimerism.
• CMA detected 3.8% more genetic abnormalities than karyotype analysis.
• Significantly higher detection rates for abnormal karyotypes and VOUS were observed in fetuses with ultrasound abnormalities compared to those without.

Conclusions:

• CMA improves the detection of fetal genetic abnormalities in cases with ultrasound structural abnormalities.
• While CMA offers benefits, a high rate of VOUS detection in the absence of ultrasound findings necessitates careful selection of indications.
• The study highlights the value of CMA as a complementary tool in prenatal genetic screening.