Chromosomal microarray (CMA) is a molecular cytogenomic tool for detecting both copy number changes (deletions and duplications) and copy-neutral regions of homozygosity (ROH) within the DNA.
Indications for Pregnancy Loss CMA
Chromosome SNP microarray can be utilized for detection of the following genomic changes:
CGL often recommends follow-up studies to further elucidate positive microarray results. Recommendations, if any, appear in the proband’s result report. Follow-up testing may include:
CMA will NOT detect balanced rearrangements (i.e. inversions, translocations, etc.), heterodisomy, or low-level mosaicism (below ~20%). It will not detect single gene point mutations or small duplications/deletions. CNVs that are smaller than the resolution of the array may not be detected or reported.
SNP CMA may reveal whole genome mosaicism suggestive of presence of two different genomes, as in the case of maternal cell contamination. The presence of maternal cell contamination may limit the interpretation of CMA results. For products of conception or placenta, when a single female genome is detected, it is assumed to represent the female fetus. However, the rare possibility that the DNA analyzed has originated in the gestational carrier cannot be excluded; GCC testing is required to rule out this possibility.
|1 Mb or larger
|2 Mb or larger
|Region of Homozygosity
|10 Mb or larger, 3 Mb and larger analyzed*
*Smaller ROH or copy number variants may be reported if demonstrated to have high clinical value.
*Patients without a preauthorization for CMA who are denied coverage by their insurance provider may be liable for the entire cost of the CMA if the Billing CMA Waiver is not signed. A signed waiver will reduce the fee by 40% if denied coverage.
Chromosome analysis is performed on G-banded metaphase chromosomes for the purpose of detecting numerical and/or structural abnormalities that may be present. These include aneuploidy (such as trisomy or monosomy), mosaicism, unbalanced rearrangements such as interstitial or terminal deletions/duplications and/or balanced rearrangements such as translocations and inversions.
For standard chromosome analysis, 15 cells are counted and 5 cells are analyzed for chromosome structure and number with at least 400-450 band level of resolution.
Duplications or deletions smaller ~5 Mb are not detectable by chromosome analysis. Chromosome analysis cannot detect Uniparental Disomy, Regions of Homozygosity (ROH), or single gene conditions.
Some chromosome abnormalities may warrant additional testing by microarray including unbalanced rearrangements, apparently balanced rearrangements in an individual with symptoms, and copy number variants to determine the extent of chromosome material involved and identify affected genes. Testing for family members may also be recommended when a chromosome rearrangement is identified.
**Please note: Chromosome analysis is only possible on living cells because cell culture is needed. An extended amount of time between fetal demise and arrival of the sample at the lab will increase the likelihood of test failure. Addition of concurrent or reflex chromosomal microarray (CMA) testing will significantly improve the chance of reportable results.
Fluorescence in situhybridization (FISH) detects chromosome copy number changes. Pregnancy Loss Trisomy FISH probes for chromosomes anomalies often seen in products of conception include X, Y, 13, 15, 16, 18, 21, and 22.
FISH is not considered a diagnostic test and cannot determine the extent of material duplicated or deleted. Diagnostic testing by chromosome analysis or chromosome microarray (CMA) is required for confirmation.
This test has historically been known as "Maternal Cell Contamination" (MCC) analysis.
Various methods of prenatal sample collection pose an increased risk for contamination with gestational carrier cells including CVS, products of conception, and other placental samples. Such contamination can result in ambiguous or even unusable results if not clarified. When not excluded by other test results, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) recommend that GCC studies be performed to optimize interpretation of the primary study molecular and/or cytogenetic results.
GCC testing by short tandem repeat (STR) analysis is performed by Colorado Molecular Correlates (CMOCO), a partner lab of Colorado Genetics Laboratory (CGL).
Gestational carrier contamination studies are performed as needed depending on the specimen provided. GCC studies are typically run concurrently with chromosome microarray, and as a reflex analysis if XX or mosaic XX results are found in the proband sample. The decision when and if to run GCC analysis will be made by CGL in conjunction with the ordering provider.
For additional information, contact CGL Client Services at (303)724-5701.
A blood or buccal sample from the carrier of the pregnancy is required for GCC testing and may be submitted along with tissue sample.
|Send 1 cm3 of any of the following samples:
|Samples will be mailed back without testing:
|· Placenta from cord insertion site
· Fetal tissue from gonad, kidney, lung, or fascia lata
· Umbilical cord ONLY when under 16 weeks for microarray
|· Intact fetuses over 10 weeks gestation
· Large fetal parts
· Samples preserved in formalin/formaldehyde
· Surgical equipment used for termination, etc.
All samples must be labeled with the patient’s name and second identifier (ex: DOB, MRN).
|Chromosome analysis and/or CMA
|1 cm3 tissue (see acceptable tissue list)
|Chromosomes: 88233, 88262, 88280, 88291
CMA: 88233, 81229
|Pregnancy Loss Trisomy FISH (part of reflex pathway with chromosomes or CMA)
|No additional sample needed
|88271 x 9, 88274 x 4, 88291
|Gestational Carrier Contamination Testing
|Peripheral Blood: 3 ml in EDTA tube
|Sample must be from the gestational carrier.
Billed by outside lab.
*Buccal swab kits available by request.