Cytogenomic microarray analysis, also known as chromosomal microarray analysis (CMA), can be used to diagnose genetic syndromes caused by chromosome deletions, chromosome duplications, or uniparental disomy (UPD). Examples include Down syndrome, DiGeorge syndrome, velocardiofacial syndrome, Williams syndrome, Prader-Willi syndrome, and unbalanced translocations.
It is typically the best diagnostic genetic test to begin with when:
- Fetal abnormalities are seen by ultrasound (ACOG Committee Opinion 581)
- There is an intrauterine fetal demise or stillbirth (ACOG Committee Opinions 581)
- A person has more than one abnormality not fitting with a known syndrome
- A person has developmental delay or intellectual disability
- A person has an autism spectrum disorder (ACMG Practice Guideline, 2010)
Ordering providers can choose whether or not variants of uncertain clinical significance are reported. The latter may be most useful for prenatal testing when ultrasound has been normal and the chance of a genetic abnormality is low. Wapner, et al. 2012 found that CMA revealed more clinically relevant chromosome deletions and duplications than did standard karyotyping, even when the reason for pursuing testing was maternal age or abnormal serum screening results.
Cytogenomic microarray analysis is done using the Illumina Infinium CytoSNP-850K BeadChip, which contains 850,000 probes for SNP markers. Analysis in the CCL is limited to detecting copy number changes (deletions and duplications) that include at least 10 probes and regions of copy number neutral absence of heterozygosity (AOH) that include at least 500 probes. Copy number changes containing no genes or found commonly in the general population are not reported. UPD is reported for telomeric regions of AOH >5Mb in length or interstitial regions of AOH >15 Mb in length. Possible identity by descent is reported when regions of AOH >3 Mb comprise ≥1.5% of the autosomal genome (approximately second cousins). Deletions and duplications of ≥400 kb are reported, even if clinical significance is unclear, as per provider request. Smaller deletions or duplications in regions of known microdeletion/microduplication syndromes or in clinically relevant genes will also be reported.
Limitations of the test: Cytogenomic microarray analysis will not detect imbalances in regions of the genome not represented on the microarray, low-level mosaicism (<20%), tetraploidy, balanced alterations (e. g. reciprocal translocations), methylation anomalies and other epigenetic events, or point mutations that may be responsible for a clinical phenotype.
- Peripheral Blood: 3-4 ml in EDTA (lavender top vacutainer). Keep at room temperature.
- Cord Blood: 1-2 ml in EDTA (lavender top vacutainer). Keep at room temperature.
- Products of Conception and Fetal Tissue: If identifiable tissue in products of conception, send chorionic villi. If material is small and unidentifiable, send entire sample. For stillbirths, send fascia lata, lung, or kidney if possible. Fresh tissue: 30-50mg in sterile transport media containing antibiotics (e.g. Alpha-MEM media, RPMI) or two T-25 flasks 80-90% confluent. Keep refrigerated. Frozen tissue (-20 degrees): 30-50 mg. Remove media before freezing. Keep frozen (-20 degrees) during transport.
- Amniotic Fluid: 15-20ml of amniotic fluid OR two T-25 flasks that are 80-90% confluent. Keep at room temperature.
- Chorionic Villi: Two T-25 flasks that are 80-90% confluent. Keep at room temperature.
- DNA: 3-10 micrograms (minimum 1 microgram) at a concentration of 100 nanograms per microliter (or higher), suspended in water. Keep at room temperature.
- Saliva: 0.5mL in Oragene•ONE(ON-500) Collection Kit. Keep at room temperature.
Return of Results: Results will be faxed to the number(s) provided on the test requisition form.
Turnaround Time: 7 to 14 days from receipt of adequate sample
- For prenatal testing, add 7 days if sample needs to be cultured (more likely if gestational age <18 weeks)
- Bloody or discolored amniotic fluid samples or amniocyte cell pellets with blood cells present will be cultured to reduce the risk of maternal cell contamination
How to Order
Please follow these steps:
Test kits and return shipping are available, as needed. Please call 206-598-8684 to request kits.
1. Complete CCL Constitutional Test Request Form, including billing information.
2. Collect sample.
3. Deliver to Clinical Cytogenomics Laboratory as soon as possible. Samples are accepted 7 days a week.
Ship sample overnight to:
c/o Cytogenetics and Genomics Laboratory
University of Washington Medical Center
Room NW-125, Box 356100
1959 NE Pacific St
Seattle, WA 98195-6100
Note: Orders cancelled after they have been submitted will incur a prorated charge based on the work that has been completed as of the time of cancellation.
Prior Insurance Authorization: When this is required by a patient’s insurance plan, we can do it for you. Download and complete the CPDx INSURANCE VERIFICATION FORM.
CPT Code & Cost81229