Test Directory

The CytoScan HD Assay is a qualitative assay intended for the postnatal, prenatal, and neoplastic detection of chromosomal copy number variants (CNV) in genomic DNA (gDNA) obtained from patients' fresh or frozen tissue biopsies, including bodily fluids (i.e. peripheral whole blood, bone marrow, lymph node, amniotic fluid, chorionic villus sampling, fetal tissue, tumor, saliva, buccal, direct/cultured cells) referred for chromosomal testing based on clinical presentation. The CytoScan HD Assay is indicated for the detection of CNVs associated with developmental delay and/or intellectual disability (DD/ID), congenital anomalies, dysmorphic features, neoplasia, and fetal anomalies. Assay results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice including confirmation by alternative methods, parental evaluation, clinical genetic evaluation, and counseling as appropriate. Interpretation of assay results is intended to be performed only by healthcare professionals board certified in clinical cytogenetics or molecular genetics. The assay is intended to be used on the CytoScan GeneChip System 3000 and analyzed by Chromosome Analysis Suite Software (ChAS Software).

This device is not intended to be used for standalone diagnostic purposes for testing or screening of postnatal, prenatal, or somatic genetic aberrations. The results should be interpreted in conjunction with standard cytogenetics and/or molecular analyses and in correlation with the patient's clinical presentation.

Specimen: Peripheral Blood, Cord Blood

Collection Container: Green Top (Sodium Heparin)

Desired Specimen Volume: 2 - 5 mL

Minimum Acceptable Volume: 1 mL

• Lithium heparin is not acceptable.
• Specimens must be collected in a sterile collection container.

Each specimen must be accompanied by a requisition form, script, electronic order or physician note. Each order must indicate the reason for testing (diagnosis).

• Transport to the laboratory at room temperature.
• Store specimen as whole blood, in original tube, at room temperature and deliver to lab within 24 hours.
• If specimen cannot be delivered within 24 hours, store in refrigerator. Do not freeze specimen.
• Specimens collected on the weekends must be refrigerated upon arrival at HNL Lab Medicine.

• Specimen frozen
• Specimen arriving without any form of patient identification (unlabeled)
• Specimen with attached needles
• Specimen arriving with broken or leaking collection tube
• Unfixed specimen treated with fixative

This analysis will not detect all types of genetic alterations including but not limited to balanced structural chromosome rearrangements (i.e. translocations, insertions, or inversions); deletions, duplications, or mosaicisms below the resolution of the CytoScan HD analysis including mutations at the base pair genetic level. Copy number variations (CNV) reported as common findings in the general population, not associated with known clinically relevant genes, or not located within a region previously reported as having diagnostic or prognostic significance are interpreted as not clinically relevant and may not be reported in this analysis. CNV are significantly detected at a resolution of >20kb spanning no less than 25 contiguous markers for losses of genomic DNA unless the copy number variant is classified as benign, does not include coding genes, or is located within the intron of a gene and >50kb spanning no less than 50 contiguous markers for gains of genomic DNA within the clinically significant gene regions represented in this CytoScan HD microarray platform. Mosaic copy number <20%may not be reliably detected and detection sensitivity is affected by the size of the CNV. Loss or absence of heterozygosity (LOH/AOH) is reliably detectable at a resolution of >3Mb. Contiguous region of homozygosity (ROH) on a single chromosome of >20Mb interstitially or >10Mb telomerically is suggestive of uniparental disomy (UPD) though this threshold may vary depending upon the location of the ROH and the overall percentage of ROH that is detected. ROHs comprising 2.5% or greater of the covered genome will be reported and it is strongly recommended that UPD follow-up testing be performed. Contiguous regions of homozygosity of >8Mb on multiple chromosomes suggests Identical By Descent (IBD) alleles which has potential increase risk for recessive disorders.

• Microarray/ SNP Array
• CMA
• Constitutional Microarray

SNP/CGH microarray analysis is performed using the Applied Biosystems CytoScane HD platform which is composed of ~1.9 million non-polymorphic oligonucleotide markers and ~750,000 single nucleotide polymorphic (SNP) markers with an average spacing of 1 marker/880bp within the known clinically significant genes and 1 marker/1.7kb between the known genes. The genomic markers are used to detect CNV and allelic imbalances which suggests loss or LOH/AOH, mosaicism, IBD,and/or UPD.