What is a chromosomal microarray analyzing copy number variations, and what is its clinical utility?

• A. CMA detects balanced rearrangements.
• B. CMA sequences the entire genome.
• C. CMA detects submicroscopic deletions and duplications; more sensitive than karyotype for CNVs; cannot detect balanced rearrangements.
• D. CMA is an imaging technique for chromosomes.

Answer: (C)

Chromosomal microarray analyzes copy number variations by scanning the genome for gains and losses in DNA dosage across many loci. This makes it much more sensitive than conventional karyotyping for detecting submicroscopic deletions and duplications that are too small to see under a light microscope.

Clinically, CMA has a high utility because it increases the diagnostic yield for individuals with developmental delay, intellectual disability, congenital anomalies, or autism by identifying pathogenic or likely pathogenic microdeletions and microduplications. Finding these CNVs can confirm a specific microdeletion/microduplication syndrome, influence prognosis, guide management, and inform genetic counseling regarding recurrence risk. In SNP-based arrays, CMA can also reveal regions of homozygosity and uniparental disomy, adding information about consanguinity or imprinting-related issues.

A key limitation to keep in mind is that CMA cannot detect balanced rearrangements, such as balanced translocations or inversions, because these do not change the overall copy number. It also does not identify single-nucleotide variants.