Chromosomal Microarray (CMA)

Chromosomal microarray analysis (CMA) is a high-resolution genome-wide assay that detects copy number variants (CNVs), deletions and duplications, across the genome. It is the recommended first-tier test for individuals with intellectual disability, autism spectrum disorder, or multiple congenital anomalies.

• aCGH (array comparative genomic hybridization): Compares patient DNA to reference DNA using differentially labeled fluorescent dyes. Detects copy number changes but NOT absence of heterozygosity (AOH).
• SNP array: Uses single nucleotide polymorphism probes. Detects both CNVs AND regions of AOH/LOH, enabling detection of uniparental disomy (UPD) and consanguinity. The same finding is reported under several names depending on the laboratory: absence of heterozygosity (AOH), loss of heterozygosity (LOH), long contiguous stretches of homozygosity (LCSH), and runs of homozygosity (ROH) all describe it. A single such region on one chromosome suggests UPD; multiple regions across several chromosomes suggest parental relatedness.
• Resolution: Typically 50-100 kb for targeted regions, 200-400 kb genome-wide. Much higher resolution than karyotype (~5-10 Mb).

• Deletions and duplications (unbalanced CNVs)
• Aneuploidy
• Regions of AOH/LOH (SNP arrays only)
• UPD (SNP arrays only, when parental samples available)

• Balanced rearrangements: Translocations, inversions (no net gain/loss)
• Low-level mosaicism: Generally requires >20% abnormal cells
• Point mutations: Single nucleotide variants
• Polyploidy: Triploidy is missed by aCGH (balanced gain across all chromosomes); SNP arrays can detect it via the abnormal B-allele frequency/allele-balance pattern

• First-tier test for unexplained ID/DD, ASD, or MCA
• Prenatal diagnosis with structural anomalies on ultrasound
• Products of conception analysis

• Results reported using ISCN nomenclature
• Example: arr[GRCh38] 7q11.23(72,726,578_74,142,672)x1 is a 1.4 Mb deletion at 7q11.23 (Williams syndrome region)