Chromosomal microarray analysis in pregnancies at risk for a molecular disorder

Area of Science:

• Prenatal Diagnosis
• Medical Genetics
• Molecular Diagnostics

Background:

• Patients referred for invasive prenatal diagnosis due to molecular disorders often undergo targeted genetic testing.
• Chromosomal microarray (CMA) is a high-resolution technique for detecting chromosomal abnormalities.
• The utility of CMA in cases with normal molecular results but specific genetic risks is not fully established.

Purpose of the Study:

• To evaluate the diagnostic yield of chromosomal microarray (CMA) in prenatal cases referred solely for molecular testing.
• To assess the value of CMA when initial genetic tests for specific molecular disorders are normal.

Main Methods:

• A 2-year prospective study involving 184 pregnant patients at risk for fetal hemoglobin Bart's disease or beta-thalassemia major.
• Patients with normal fetal genotype results opted for CMA testing.
• CytoScan 750 K array was utilized for CMA analysis.

Main Results:

• In 184 patients with normal molecular results, CMA identified unexpected de novo pathogenic microdeletions in 1.1% of cases.
• Identified microdeletions included 22q11.21 (3.2 Mb) and 16p11.2 (0.8 Mb).
• Median maternal age was 29 years and median gestational age was 13 weeks.

Conclusions:

• Chromosomal microarray (CMA) offers additional diagnostic value in pregnancies at risk for thalassemia, beyond molecular testing.
• The findings suggest that CMA should be considered as part of comprehensive pretest counseling for prenatal diagnostic testing.
• Integrating CMA into counseling may improve detection of chromosomal abnormalities in specific at-risk populations.