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 Prenatal 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.
CMA may reveal whole genome mosaicism suggestive of the presence of two different genomes, as in the case of contamination with cells from the gestational carrier (GCC), which may limit the interpretation of CMA results. For products of conception, placenta or chorionic villi samples, 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 will 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.
Standard (Routine) Chromosome Analysis
5-cell Chromosome Analysis
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.
Fluorescence in situ hybridization (FISH) detects chromosome aneuploidy and submicroscopic genomic copy number changes such as deletions and duplications in specific regions.
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 is required. See ordering options below.
Occasionally, FISH may be recommended to clarify the results of chromosome analysis or microarray. Such additional recommendations will be discussed with the ordering provider prior to being performed.
Amniotic fluid alpha-fetoprotein (AF-AFP) testing at 15-30 weeks gestation screens a fetus for an increased risk of open neural tube or open body wall defects. AF-AFP analysis can be used to further evaluate abnormal serum AFP levels identified during maternal serum screening. Acetylcholinesterase (AChE) testing is performed as a reflex confirmation test on individuals with an abnormal amniotic fluid alpha-fetoprotein (AF-AFP) level of 2.0 multiples of the mean (MOM) or greater.
AF-AFP testing is performed by the Associated Regional University Pathologists, Inc. (ARUP). Results and interpretation of the AChE are provided to the Colorado Genetics Laboratory by Associated Regional University Pathologists, Inc. (ARUP) and the Foundation for Blood Research (FBR).
afAFP and AChE testing cannot be performed on a chorionic villi sample and require an amniotic fluid sample between 15-30 weeks gestation. Positive/abnormal results from this testing are not specific to a certain genetic or physical diagnosis, but contribute to the overall clinical likelihood of a disorder.