Clinical Applications of Chromosomal Microarray Analysis

ABSTRACT

Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.