TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: CMAP    
Chromosomal Microarray, Prenatal, Amniotic Fluid/Chorionic Villus Sampling

Useful For Suggests clinical disorders or settings where the test may be helpful

Prenatal diagnosis of copy number changes (gains or losses) across the entire genome

 

Determining the size, precise breakpoints, gene content, and any unappreciated complexity of abnormalities detected by other methods such as conventional chromosome and fluorescence in situ hybridization (FISH) studies

 

Determining if apparently balanced abnormalities identified by previous conventional chromosome studies have cryptic imbalances, since a proportion of such rearrangements that appear balanced at the resolution of a chromosome study are actually unbalanced when analyzed by higher-resolution chromosomal microarray

 

Assessing regions of homozygosity related to uniparental disomy or identity by descent

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

Cultures from this specimen will be discarded 10 days after all cytogenetic test results have been reported. If further testing is desired, call the laboratory at 507-284-1668.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Maternal cell contamination (MCC) testing will be performed at no additional charge if a maternal blood sample is received to rule out the presence of maternal cells in the prenatal sample, see Additional Testing Requirements.

 

If an insufficient sample is received or MCC is identified in the prenatal sample, microarray testing will be performed on cultured material.

 

The following algorithms are available in Special Instructions:

-Prenatal Aneuploidy Screening and Diagnostic Testing Options

-High-Risk Pregnancy Based on Fetal Malformations or Positive Serum Screen: Laboratory Testing Algorithm

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Chromosomal abnormalities cause a wide range of disorders associated with birth defects and intellectual disability. Many of these disorders can be diagnosed prenatally by analysis of chorionic villi or amniocytes.

 

The most common reasons for performing cytogenetic studies for prenatal diagnosis include advanced maternal age, abnormal prenatal screen, a previous child with a chromosome abnormality, abnormal fetal ultrasound, or a family history of a chromosome abnormality. Chromosomal microarray (CMA) is a high-resolution method for detecting copy number changes (gains or losses) across the entire genome in a single assay and is sometimes called a molecular karyotype. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommend the chromosomal microarray as a replacement for the fetal karyotype in patients with a pregnancy demonstrating one or more major structural abnormalities on ultrasound when undergoing invasive prenatal diagnosis.(1)

 

This CMA test utilizes more than 1.9 million copy number probes and approximately 750,000 single nucleotide polymorphism probes for the detection of copy number changes and regions with absence of heterozygosity. Identification of regions of excessive homozygosity on a single chromosome could suggest uniparental disomy, which may warrant further clinical investigation when observed on chromosomes with known imprinting disorders. In addition, the detection of excessive homozygosity on multiple chromosomes may suggest consanguinity.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Copy number variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

When interpreting results it is important to realize that copy number variation is found in all individuals, including patients with abnormal phenotypes and normal populations. Therefore, determining the clinical significance of a rare or novel copy number change can be challenging. Parental testing may be necessary to further assess the potential pathogenicity of a copy number change.

 

While most copy number changes observed by chromosomal microarray testing can readily be characterized as pathogenic or benign, there are limited data available to support definitive classification of a subset into either of these categories. In these situations, a number of considerations are taken into account to help interpret results including the size and gene content of the imbalance, whether the change is a deletion or duplication, the inheritance pattern, and the clinical and developmental history of a transmitting parent.

 

All copy number variants within the limit of detection classified as pathogenic or likely pathogenic will be reported regardless of size. This includes but is not limited to incidental findings currently recommended for reporting by the American College of Medical Genetics and Genomics (ACMG).(2) Copy number changes with unknown significance will be reported when at least one protein-coding gene is involved in a deletion greater than 1 megabase (Mb) or a duplication greater than 2 Mb.

 

The detection of excessive homozygosity may suggest the need for additional clinical testing to confirm uniparental disomy (UPD) or to test for variants in genes associated with autosomal recessive disorders consistent with the patient's clinical presentation that are present in regions of homozygosity. Regions with absence of heterozygosity (AOH) of unknown significance will be reported when greater than 5 Mb (terminal) and 10 Mb (interstitial) on UPD-associated chromosomes. Whole genome AOH will be reported when greater than 10% of the genome.

 

The continual discovery of novel copy number variation and published clinical reports means that the interpretation of any given copy number change may evolve with increased scientific understanding.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test does not detect all types and instances of uniparental disomy.

 

This test is not designed to detect low-level mosaicism, although it can be detected in some cases.

 

This test does not detect point alterations, small deletions or insertions below the resolution of this assay, or other types of variants such as epigenetic changes.

 

The results of this test may reveal incidental findings not related to the original reason for referral. In such cases, studies of additional family members may be required to help interpret the results.

Supportive Data

The array was validated by testing 40 prenatal specimens (direct and cultured amniotic fluid and chorionic villus samples) previously tested using chromosome analysis, fluorescence in situ hybridization (FISH) analysis, or a polymerase chain reaction (PCR)-based assay. All abnormalities previously identified by another methodology were confirmed.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. American College of Obstetricians and Gynecologists Committee on Genetics. Committee opinion no. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013;122:1374-1377

2. Kalia, S., Adelman, K., Bale, S. et al: Recommendations for reporting of secondary findings in clinical exome and genome sequencing. 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017;19:249-255

3. Wapner RJ, Martin CL, Levy B, et al: Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367:2175-2184

4. Armengol L, Nevado J, Serra-Juhe C, et al: Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis. Hum Genet. 2012;131:513-523

5. Breman A, Pursley AN, Hixson P, et al: Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature. Prenat Diagn. 2012;32:351-361

6. South ST, Lee C, Lamb AN, et al: ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med. 2013;15:903-909

Special Instructions Library of PDFs including pertinent information and forms related to the test