Chromosome Array (ACGH), Prenatal


CHROMOSOME ARRAY (aCGH), PRENATAL
 
TURNAROUND TIME:     14 days
 
TESTING METHODOLOGY: Array Comparative Genomic Hybridization
 
SPECIMEN REQUIREMENTS:
    • Collect: 20-30 mL amniotic fluid in sterile centrifuge tubes or bottles; discard the first 2 mL collected to reduce risk of maternal cell contamination; or 20 -30 mg of CVS in sterile transport media.
    • Min. Collection: 16 mL amniotic fluid; 15 mg CVS
    • Collect: 3-5 mL peripheral blood in sodium heparin (green) from both parents and 3-5 mL peripheral blood in EDTA (purple) from the mother
    • Remarks: The parents’ specimens are used to interpret abnormalities found in fetal specimens when necessary; the mother’s specimen is used to rule out maternal cell contamination
    • Transport: Amniotic fluid, CVS,peripheral blood in EDTA (purple) and sodium heparin (green) at room temperature
    • Stability: Ambient: 24 hours; Refrigerated: 24 hours
    • Unacceptable Conditions: Frozen, fixed or non-sterile specimens; clotted blood specimens; blood specimens in anticoagulants other than EDTA and sodium heparin
    • A Prenatal Diagnosis Information Form and a Cytogenetics Laboratory Test Requisition must accompany the specimen. Contact the Cytogenetics Laboratory at 918-502-1722 to obtain further information.
    • Parental testing policy: Parental testing is recommended when a fetus is found to have an abnormality. Parental analysis may clarify the clinical significance of a copy number change and it is used to access the inheritance of the abnormality (familial or de novo). For a copy number change of unclear clinical significance, parental FISH testing is free. For clinically significant abnormalities, parental FISH analysis is available as a separate test for an additional cost. Parental array testing is also considered a separate test with an additional cost.
    • Maternal cell contamination (MCC): MCC testing is recommended  for all prenatal DNA-based testing on amniotic fluid to insure accuracy of the test results; MCC testing is required for CVS specimens due to the difficulty of removing all maternal decidua from villi and thus the substantial risk of MCC
Test Summary:
Test can detect copy number variations (gains and losses) throughout the genome. The array covers almost 1,000 gene regions important in development and over 245 recognized genetic syndromes. The array has a minimum average resolution of 35 kilobases across the entire genome. In addition, a higher resolution coverage of approximately 10 kilobases is in the targeted regions. These include regions involved in common microdeletion and micoduplication syndromes, genes associated with Mendelian disorders and the subtelomeric and pericentromeric regions of the chromosomes. The array also contains 60,000 SNP probes that can provide information about some types of uniparental disomy.

Related Tests: Chromosome Analysis, Amniotic Fluid; FISH Analysis, Prenatal Aneuploidy Screen

Methods:Microarray analysisusing an array of 135,000 oligonucleotide probes including 60,000 SNP probes throughout the genome; abnormalities are confirmed by fluorescence in situ hybridization (FISH)  

Interpretation: An abnormal (clinically significant) result is reported when an abnormality (gain or loss) is associated with a known Mendelian disorder, a recognized microdeletion or microduplication syndrome or an unbalanced chromosome rearrangement. The results of this test may also be of unclear clinical significance. In these cases, studies of parents may be required to assist in interpreting the results. Consultation with a genetic professional is recommended for test interpretation.

Test Limitations: Balanced chromosomal rearrangements (reciprocal translocations, Robertsonian translocations, inversions and balanced insertions) and imbalances of regions not represented on the microarray will not be detected. This microarray is not designed to detect mosaicism. A normal result does not exclude the diagnosis of any of the disorders represented on the microarray since the percentage of patients who will demonstrate an alteration varies depending on the locus.

Test Variables: Turnaround time will be longer if confirmation of an abnormality by FISH and/or parental testing are necessary

FDA Approval: This test is not approved by the FDA and it should used as an adjunct to other clinical information.

Indications for Use:

  • Abnormal ultrasound findings
  • Family history of known or suspected chromosome imbalance
  • Suspected deletion or duplication syndrome
  • Inconclusive fetal karyotype result
  • Abnormal maternal serum screening result
  • Advanced maternal age

ADDITIONAL RESOURCES:

Genetics Home Reference:

  1. Chromosomes:  http://ghr.nlm.nih.gov/chromosomes
  2. Chromosome Arrays: http://ghr.nlm.nih.gov/glossary=comparativegenomichybridization