Single nucleotide polymorphism (SNP) based chromosomal
microarray (CMA) is a powerful cytogenomic tool for detecting both copy number
variation (deletions or duplications) and copy-neutral structural variants such
as regions of homozygosity (ROH) and uniparental disomy (UPD). Detection of submicroscopic
abnormalities, including microdeletions and microduplication, may be missed by standard chromosome
analysis. The addition of a 5 cell chromosome analysis
evaluates chromosomes for balanced rearrangements such as inversions and
Features of the Infinium®
CytoSNP-850K BeadChip Array
High resolution array containing 850,000 SNPs with ~15x redundancy of each marker
Follows the International Collaboration for Clinical Genomics (ICCG) guidelines for chip design
Probes spaced ~1.8 kb along genome for a resolution of ~10kb
Targets microdeletion/microduplication syndrome regions with enriched coverage for more than 3,200 known disease genes
Regions of homozygosity (ROH) evaluated for possible uniparental disomy (UPD) and recent shared ancestry
A consensus statement by International Collaboration for Clinical
Genomics (ICCG) recommends that CMA should be the first tier test
for individuals with 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.
Standard cytogenetic evaluation will
help detect abnormal structural rearrangements in the chromosomes, such as
translocations and inversions, identifying possible balanced translocation
Patient DNA is obtained by extraction from peripheral
white blood cells. The CytoSNP-850K
assay utilizes an amplification step for the DNA and hybridizes this to the
BeadChip. The assay then uses a labeling process to provide allele and
intensity data. BeadChips are scanned using a two-channel high-resolution laser
imager and analyzed using Illumina software.
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 CNVS listed
in the Database of Genomic Variants are not reported. While NOT diagnostic, SNP
data allows for detection of regions of homozygosity (ROH) suggestive of UPD
(isodisomy) or shared ancestry (consanguinity) with possible implications in
the context of recessive disorders. ROH is evaluated at ≥5 Mb with a reporting
threshold of ~10 MB. Total percentage of ROH is reported when ≥5%.
For the cytogenetic analysis, a
minimum of 5 metaphases are examined and 2 karyotypes are prepared at >550
CMA will not detect balanced rearrangements
(i.e., inversions, translocations), heterodisomy, or very low level mosaicism. It
will not detect single gene mutations such as single nucleotide
mutations/polymorphisms. Abnormalities that are smaller than the resolution of
the array may not be detected.
The 5 cell standard
cytogenetic analysis will not detect very subtle chromosomal rearrangements and
will not adequately detect possible mosaicism.
Submit peripheral blood in two tubes: a minimum of 2 ml in an EDTA purple top tube and a minimum of 3 ml in a sodium heparin green top tube.
When 5 ml of peripheral blood cannot be obtained (e.g., in babies), 3 ml peripheral blood in a sodium heparin, green top tube alone is acceptable.
Label specimen tubes with patient's name and a second identifier.
Hold specimen at room temperature and transport to the Colorado Genetics Laboratory as soon as possible.
Detailed written report provided with genetic
counseling phone consultation available to medical providers.
Autism referrals cross-referenced with current
autism database(s) for up-to-date copy number associations.
Microarray Billing Policy Effective June 1, 2014
new molecular CPT codes became effective January 1, 2013, insurance companies
subsequently revised their medical policies regarding medical necessity for
chromosomal microarray. Because of the
variability among these policies, waivers for microarray testing have been
implemented for all insurance carriers, except Colorado Medicaid.
have your patient complete and sign the Waiver for CytoSNP-850K Microarray form
below, and submit it with the specimen for microarray testing. If the patient’s insurance denies the
charges, the patient will be billed at a discounted rate.
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.