Constitutional Cytogenetics SNP Microarray – Products of Conception

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 sequence 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).

Recently, the American College of Obstetricians and Gynecologists issued a committee opinion statement concerning microarray and products of conception:   “In cases of intrauterine fetal demise or stillbirth when further cytogenetic analysis is desired, chromosomal microarray analysis on fetal tissue (ie, amniotic fluid, placenta, or products of conception is recommended because of its increased likelihood of obtaining results and improved detection of causative abnormalities…Limited data are available on the clinical utility of chromosomal microarray analysis to evaluate first-trimester and second-trimester pregnancy losses; therefore, this is not recommended at this time.”¹  

Note: Targeted flourescent in situ hybridization (FISH) or chromosome analysis may be a better option for first and second trimester pregnancy losses – please contact our lab.  With suboptimal sample or where there is a concern for growth in culture, microarray may be useful.

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

Indications:

SNP based microarray testing is indicated in the following circumstances:

Intrauterine fetal demise or stillbirth
Pregnancy loss or termination in the presence of fetal anomalies
Further characterization of fetal chromosomal abnormalities seen by conventional cytogenetic analysis
Multiple fetal losses of unknown etiology
POC samples that fail to grown in culture
Partial or complete molar pregnancy

DNA is extracted from uncultured products of conception, fluorescently labeled and hybridized (with labeled reference DNA) to an Oxford Genome Technology-designed ISCA +SNP 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 (Riggs et al. 2019).   Any changes associated with LCSH will be reported according to professional practice standards and guidelines.²

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

• Abnormal copy number findings are confirmed at NO CHARGE using an independent technique, when possible.
• Targeted parental studies for reported copy number findings will be performed at NO CHARGE using an independent technique, when possible.

HANDLE ALL SPECIMENS ASEPTICALLY.  KEEP SAMPLES AT ROOM TEMPERATURE AND TRANSPORT TO LABORATORY AS SOON AS POSSIBLE.

Tissue choices:
 
If no identifiable fetus is present (e.g. missed abortion):

1. Entire specimen
2. Biopsy of fetal side of placenta (e.g. villi)
3. Fetal membranes 

If fetal demise, stillbirth, or neonatal demise:

1. Amniotic fluid may be collected prior to elective termination.  (See information for Chromosomal Microarray-Prenatal Diagnosis for instructions.)
2. Biopsy of fetal side of placenta (e.g. villi) - preferred
3. Skin:  deep tissue sample, at least 3 cubic mm – preferred
4. In addition to the above, other tissues may be acceptable.  Please contact our lab to discuss your options.  Ask to speak with a Microarray Technologist. 

DO NOT PLACE IN FORMALIN.  Tissue must be suspended in sterile culture media (e.g. RPMI, α-MEM,   Ham’s F-10) or tissue transport media supplied by our lab.  If none of these are available you may use the following:  sterile Ringer’s solution, sterile normal saline. 

Maternal blood must accompany your POC sample: 3ml in EDTA.   FISH for fetal gender determination will be performed and if a maternal cell contamination study is deemed necessary, it will be performed at no additional charge.   

Molar Pregnancy:  If a molar pregnancy is suspected, then paternal blood is recommended for STR analysis: 3ml in EDTA.  

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

Mon-Sat

14-21 days (Note: Routine cases will be reported at the low-end of our turnaround time range; 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. 
• Shipping supplies can be provided to you upon request.    
• DO NOT use the cold pack provided in the KDL shipping kit. 
• Ship the specimen overnight express, using the FedEx priority overnight label provided with the KDL shipping kit.  The specimen must arrive at the lab no more than 24 hours after collection. 
• Contact Client Services at (855) 535-1522 if you need shipping supplies or additional instructions.

1. ACOG/SMFM committee opinion on microarray testing.
2. 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.
3. Riggs et al. 2019 Genet Med; doi.org/10.1038/s41436-019-0686-8