Chromosomal microarray (CMA) is a molecular cytogenomic tool for detecting both copy number changes (deletions and duplications) and copy-neutral regions of homozygosity (ROH).
- Infinium® CytoSNP-850K BeadChip Array
- 850,000 SNPs with ~15x redundancy of each marker.
- Probes spaced ~1.8 kb and average resolution of ~10 kb.
- Targets microdeletion/microduplication syndrome regions with enriched coverage for more than 3,200 known disease genes.
- Detect regions of homozygosity (ROH) resulted from uniparental disomy (UPD) or identity by descent.
Indications
ACMG recommends CMA as the first-tier test for individuals with unexplained developmental disabilities, intellectual disabilities, autism spectrum disorders, or multiple congenital anomalies. CMA testing is also indicated for individuals with seizures and other developmental problems for which a genomic basis is suspected.
If karyotype analysis has not been performed previously, 5-cell chromosome analysis, on peripheral blood or tissue, is recommended with the microarray testing to rule out possible balanced structural rearrangements such as translocations, inversions and insertions. In cases of imbalances detected by CMA, karyotype analysis may be helpful to reveal mechanisms underlining the copy number changes. For details see Pediatric and Adult (Postnatal) Microarray and 5 Cell Chromosomes Analysis below.
CMA reporting criteria
For reporting of copy number variations (CNVs), thresholds are ≥200 kb for deletions and ≥400 kb for duplications with reporting of smaller findings in clinically significant regions. Common benign CNVs in general populations are usually not reported. ROH is evaluated at ≥5 Mb with a reporting threshold of ~10 MB. Total percentage of ROH is reported when ≥5%.
Disclaimer
CMA does not detect balanced structural rearrangements, heterodisomy, or low level mosaicism. It does not detect small genetic aberrations including single nucleotide mutations. .
Follow-Up Testing
Colorado Genetics Laboratory recommends that parental/familial testing be considered when a genomic imbalance is detected by chromosomal microarray. Please see current policy – Familial Follow-up for Microarray Testing Effective June 1, 2014.
References
Kearney HM, et al. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 13:680-5, 2011.
Miller DT, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 86:749-64, 2010.
South ST, et al. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med. 15:901-9, 2013.
