Constitutional Cytogenetics Chromosomal Microarray - Postnatal

*Update, March 20, 2020: The laboratory will no longer be requesting the immediate collection of NaHep blood for new microarray tests. We will continue to work closely with providers for those cases where NaHep blood will be required for confirmatory testing. The impact of this change is anticipated to be very minimal. Please contact us with any questions or for more information.

Chromosomal microarray (CMA), also known as array comparative genomic hybridization (aCGH), is a molecular technique that relies on a competition between labeled patient and reference DNA for hybridization to an array of immobilized target sequences.  CMA facilitates the simultaneous detection of thousands of target sequences and has become the gold standard for assessment of genomic imbalance, particularly submicroscopic imbalance (<5Mb).  Our SNP array is based on the ISCA 60K oligonucleotide + 120K SNP design and can detect both copy number changes and long contiguous stretches of homozygosity (LCSH) which can reflect uniparental disomy, among others (see ‘Methodology’ below).  

A recent meta-analysis published under the auspices of the ISCA (International Standards for Cytogenomic Arrays) consortium estimated an approximately 12% greater diagnostic yield with CMA over conventional karyotype for the investigation of developmental delay and intellectual disability (DD/ID), multiple congenital anomalies, and autism spectrum disorders (Miller et al. 2010).  The American College of Medical Genetics has recently recommended CMA as a first-line test for individuals with “A) Multiple anomalies not specific to a well-delineated genetic syndrome. B) Apparently non-syndromic DD/ID. C) Autism spectrum disorders” (Manning and Hudgins 2010). 

Please note: This test will not currently detect balanced chromosome rearrangements or very low-level mosaicism.

DNA is extracted from peripheral lymphocytes, fluorescently labeled and hybridized (with labeled reference DNA) to an Oxford Genome Technology-designed ISCA array, printed by Agilent.   The ISCA+ SNP array is comprised of a collection of specific probes that enable a high resolution analysis for copy number change detections for a variety of genetic disorders in ISCA defined regions.  This array combines oligonucleotide probes for accurate copy number detections with single nucleotide polymorphism (SNP) probes to detect long contiguous stretches of homozygosity (LCSH), which may reveal uniparental disomy (UPD), identity by descent (IBD) and consanguinity. Any statistically-significant genetic changes are compared against all known databases and relevant literature.  Any changes associated with LCSH will be reported according to professional practice standards and guidelines.⁴  Any statistically-significant genetic changes are compared against all known databases and relevant literature (Riggs et al. 2019). 

Reports include comprehensive interpretation and recommendations by ABMG-certified Clinical Cytogeneticists.  

• Abnormal copy number findings can be confirmed at NO CHARGE using an independent technique, when possible. A new sample will be required.
• Targeted parental studies for reported copy number findings can be performed at NO CHARGE using an independent technique, when possible. Parental samples will be required.

Blood:  An EDTA sample is required for testing*

• Adult: 3-5 mL drawn into a PURPLE top EDTA vacutainer tube.
• Child: 1-2 mL, otherwise as above.
• Infant: 1-2 mL, otherwise as above. 
• Keep at room temperature and transport to laboratory as soon as possible.
• Contact Client Services at (855) 535-1522 for supplies and instructions.

Special note for patients who have received blood products.

• For recipients of packed red blood cells or platelets, please wait at least 2 weeks to draw blood for this test. 
• For recipients of whole blood products, please wait 4 weeks to draw blood for this test. 

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Mon - Sat

10-18 days (Note: in rare cases, turnaround times may be longer because of confirmation studies – the referring clinician will be kept abreast of the situation.)

• Keep specimen at room temperature during transit.
• Contact Client Services at (855) 535-1522 for shipping kits and instructions.
• Do not use the cold pack which may be included in the KDL shipping kit.
• Ship via overnight express, using the FedEx priority overnight label provided. 
• The specimen must arrive at the lab no more than 24 hours after collection.

1. Miller et al. 2010 AJHG 86, 749-764
2. Manning and Hudgins 2010 Professional Practice and Guidelines Committee.  Genet Med. 12, 742-745.
3. ISCA: The International Standards For Cytogenomic Arrays Consortium  https://www.iscaconsortium.org/
4. Rehder et al. American College of Medical Genetics and Genomics: standards and guidelines for documenting suspected consanguinity as an incidental finding of genomic testing. Genet Med 2013 15, 150-152.
5. Riggs et al. 2020 Genet Med; doi: 10.1038/s41436-019-0686-8.

After hours, please leave message at (855) 535-1522 for the on call cytogenetic technologist.