Prenatal SNP Array Karyotyping, Prenatal Chromosome Microarray Analysis (CMA)
EPIC: LAB6770, SOFT: GSNPP
CMA cannot detect:
- Balanced chromosome rearrangements such as translocations, balanced insertions, or inversions.
- Low-level mosaicism.
- An abnormality in a region not represented on the array.
Specimen Collection Criteria
Collect: Amniotic fluid or tissue (chorionic villus tissue, fetal tissue, fetal membrane, umbilical cord) sample.
Collect specimen as follows:
- Amniotic Fluid: Collect 20-30 mL amniotic fluid into sterile 15 mL centrifuge tubes.
- Chorionic Villus Sampling: Collect 10 mg chorionic villus tissue and place into a sterile 15 mL centrifuge tube containing tissue culture transport medium.
- Products of Conception: Collect 1.0 x 1.0 cm piece of tissue (chorionic villus tissue, fetal tissue, fetal membrane, umbilical cord) and place into a sterile 15 mL centrifuge tube containing tissue culture transport medium.
- T-25 Flasks: Amniotic fluid cells, chorionic villus cells, or products of conception cells in two sterile, confluent T-25 flasks containing tissue culture transport medium.
Additionally, collect 3-5 mL of maternal peripheral blood in one Lavender-top EDTA tube with each specimen type for maternal contamination studies, if needed.
Physician Office/Drawsite Specimen Preparation
Do not freeze specimen. Store all specimen types at room temperature (20-26°C or 68-78.8°F) prior to courier pickup. For delays in transport (greater than 24 hours from the time of collection), refrigerate (2-8°C or 36-46°F) the specimen.
Preparation for Courier Transport
Transport: All specimen types, in containers as described above, at room temperature (20-26°C or 68-78.8°F).
- Improperly labeled specimens.
- Frozen specimens.
- Cracked or compromised specimens tubes.
- Specimens received greater than 72 hours past the time of collection.
Specimen Stability for Testing:
Room Temperature (20-26°C or 68-78.8°F): 24 hours
Refrigerated (2-8°C or 36-46°F): 72 hours
Frozen (-20°C/-4°F or below): Unacceptable
Specimen Storage in Department Prior to Disposal:
Refrigerated (2-8°C or 36-46°F): 7 days. A backup culture is maintained for two weeks past sign-out of the final report.
Royal Oak Cytogenetics Laboratory.
Monday - Friday.
Results available in 14 days.
Additional time may be needed for reflex testing of abnormal results.
Positive or negative for chromosome abnormality. A comprehensive interpretative report will be provided.
Affymetrix CytoScan HD Single Nucleotide Polymorphism (SNP) Array.
Results reported for:
- Deletions of duplications larger than 500kb across the genome; Deletions greater than 50kb and duplications greater than 100kb in known syndromic regions.
- No susceptibility genes are reported unless they are associated with an unambiguous outcome.
- Uniparental disomy or clear consanguinity.
Conventional cytogenetic analysis (karyotyping) permits an analysis of the entire human genome, but does so at a relatively low-level of resolution (5-10 Mb). While this is more than adequate to diagnosis many constitutional cytogenetic disorders, such as trisomy 21 (Down syndrome), it will fail to identify smaller abnormalities which may be associated with significant genetic morbidity. Fluorescence in situ hybridization (FISH) provides a much higher level of resolution (150kb), but interrogates only a specific region of the genome. Chromosome microarray analysis (CMA) provides a genome-wide assessment of copy number changes (deletions and duplications) at a resolution far greater than what is achievable with other cytogenetic methodologies such as karyotyping and FISH. CMA is now considered a first-line test, replacing the karyotype, in children with developmental delay/intellectual disability, multiple congenital anomalies, dysmorphic features, and autism/autism spectrum disorder. Several recent multicenter studies have demonstrated the utility of prenatal CMA. In one study which compared karyotyping with CMA in 4406 women (Wappner et al, 2012), clinically significant deletions and duplications were identified in 1.7% of cases with a normal karyotype referred for advanced maternal age or a positive screening result. If a structural fetal anomaly was identified by ultrasound, a clinically significant copy number change was observed in 6.0% of cases. In another study (Shaffer et al, 2012), the overall detection rate of clinically significant deletions or duplications was 5.3% for any indication for study and 6.5% for pregnancies with one or more fetal ultrasound anomalies. As in the previous study, many of the genomic changes identified by CMA were below the level of resolution achievable by karyotyping. At Beaumont, the CMA test utilizes the Affymetrix CytoScan HD single nucleotide polymorphism (SNP) array which can reliably detect 25-50 kb copy number changes across the genome. With more than two million copy number markers, including 750,000 SNPs, the Beaumont CytoScan Array offers high-density resolution of the entire genome. The Beaumont SNP array can also provide genotype information that allows for detection of uniparental disomy and consanguinity. Prenatal CMA should be considered in any pregnancy with one or more fetal ultrasound anomalies and a normal karyotype.
- Wapner, RJ et al (2012): NEJM 367(23), 2175-2184.
- Shaffer, LG et al (2012): Prenatal Diagn 32: 976-985.
- Shaffer, LG et al (2012): Prenatal Diagn 32: 986-995.
Note: This test requires insurance preauthorization. The Laboratory will not accept the specimen without preauthorization. Also note that CMA is generally performed in the outpatient setting.
EPIC: LAB6770, SOFT: GSNPP