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Pregnancy Loss Microarray


Single nucleotide polymorphism (SNP) based chromosomal microarray (CMA) is a powerful cytogenomic tool for detecting both copy number variation (deletions or duplications) and copy-neutral structural variants such as regions of homozygosity (ROH) and uniparental disomy (UPD). Detection of submicroscopic abnormalities, including microdeletions and microduplications, may be missed by standard and high resolution chromosome analysis.

 
Features of the Infinium® CytoSNP-850K BeadChip Array 
  • High resolution array containing 850,000 SNPs with ~15x redundancy of each marker
  • Follows the International Standard Cytogenomic Arrays (ISCA) consortium guidelines for chip design
  • Features are spaced ~16 kb along the backbone of the genome
  • Probes spaced ~1.8 kb along genome for a resolution of ~10kb
  • Targets microdeletion/microduplication syndrome regions with enriched coverage for more than 3,200 known disease genes
  • Regions of homozygosity (ROH) evaluated for possible uniparental disomy (UPD) and recent shared ancestry
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Indications
  • Spontaneous fetal loss at any gestational age
  • Induced termination due to fetal anomalies
  • Fetal loss with abnormal karyotype requiring further characterization
  • Fetal loss when conventional chromosome analysis cannot be obtained (due to cultulre failure)


If clinically relevant, common aneuploidies, such as Down syndrome or Trisomy 18, should be ruled out by chromosome analysis or fluorescence in situ hybridization before CMA testing is pursued.

 

Methodology

DNA is obtained by extraction from fetal tissue, products of conception and/or placenta.  The CytoSNP-850K assay utilizes an amplification step for the DNA and hybridizes this to the BeadChip. The assay then uses a labeling process to provide allele and intensity data. BeadChips are scanned using a two-channel high-resolution laser imager and analyzed using Illumina software. 

For reporting of copy number variations (CNVs), thresholds are ≥1 Mb for deletions and ≥2 Mb for duplications with reporting of smaller findings in clinically significant regions. Common CNVs listed in the Database of Genomic Variants are not reported. While NOT diagnostic, SNP data allows for detection of regions of homozygosity (ROH) suggestive of UPD (isodisomy) or shared ancestry (consanguinity) with possible implications in the context of recessive disorders. ROH is evaluated at ≥5 Mb with a reporting threshold of ~10 MB. Total percentage of ROH is reported when ≥5%.

 

Limitations

CMA will not detect balanced rearrangements (i.e., inversions, translocations), heterodisomy, or very low level mosaicism. It will not detect single gene mutations, such as single nucleotide mutations/polymorphisms. Abnormalities that are smaller than the resolution of the array may not be detected.

SNP CMA can detect whole genome mosaicism suggestive of two different genomic cell lines, as in the case of maternal cell contamination.  The presence of maternal cell contamination may limit the interpretation of CMA results.

 

Specimen Requirements

Fetal tissue is preferred in order to minimize the possibility of maternal cell contamination.

Fetal tissue (preferred)
  • Submit 0.5 cm3 fetal tissue in a sterile, plastic, screw-top tube filled with sterile transport media. CGL can provide this media.

  • Label specimen tubes with patient's name and a second identifier.
  • Hold specimen at room temperature and transport to the Colorado Genetics Laboratory as soon as possible. Refrigerate if held overnight.

 

Products of conception or placenta

  • Submit 0.5 cm3 products of conception or placenta in a sterile, plastic, screw-top tube filled with sterile transport media. CGL can provide this media.
  • Label specimen tubes with patient’s name and a second identifier.
  • Hold specimen at room temperature and transport to the Colorado Genetics Laboratory as soon as possible. Refrigerate if held overnight.
 
Samples must be accompanied by a completed Test Request Form​​ and Waiver for CytoSNP-850K Microarray. Indicate chromosomal microarray testing and include alll pertinent medical and family history.
 
Interpretation Services

Detailed written report provided with genetic counseling phone consultation available to medical providers.

 

Follow-Up Testing

Colorado Genetics Laboratory recommends that parental/familial testing be considered when a genomic imbalance is detected by chromosomal microarray. Please see current policy – Familial Follow-up After Abnormal Microarray Effective June 1, 2014.

 

Microarray Billing Policy Effective June 1, 2014

When the new molecular CPT codes became effective January 1, 2013, insurance companies subsequently revised their medical policies regarding medical necessity for chromosomal microarray. Because of the variability among these policies, waivers for microarray testing have been implemented for all insurance carriers, except Colorado Medicaid. Please have your patient complete and sign the Waiver for CytoSNP-850K Microarray form below, and submit it with the specimen for microarray testing. If the patient’s insurance denies the charges, the patient will be billed at a discounted rate.

 
Reference
Reddy UM, et al., Karyotype versus Microarray Testing for Genetic Abnormalities after Stillbirth.  The New England Journal of Medicine 367:23:2185-2193, 2013.