鈥婥hromosome analysis is performed to detect numerical and structural abnormalities such as: Trisomies, monosomies, large interstitial or terminal deletions and duplications, translocations, inversions, and mosaicism.
Turn Around Time
Generally 7-12 days
FISH for screening common aneuploidies is available in conjunction with chromosome analysis. Please refer to Fish Test List.
Turn Around Time
Average 24-48 hours.
Chromosomal microarray (CMA) is a molecular cytogenomic tool for detecting both copy number changes (deletions and duplications) and copy-neutral regions of homozygosity (ROH).
Infinium® CytoSNP-850K BeadChip Array
Prenatal CMA testing options:
Indications for prenatal CMA
Pregnancy loss CMA test options:
Indications for pregnancy loss CMA
Methodology
Patient DNA is obtained by extraction from direct amniotic fluid, cultured amniocytes, direct chorionic villi sample (CVS) or cultured CVS. The CytoSNP-850K assay includes DNA amplification, a labeling process to provide allele and intensity data, followed by hybridization to the BeadChip array. BeadChips are scanned using a two-channel high-resolution laser imager and analyzed using BlueFusionstudio software.
For reporting of copy number variations (CNVs), thresholds are ≥1 Mb for deletions/losses and ≥2 Mb for duplications/gains. Smaller findings in clinically significant regions may also be reported. Common CNVs listed in the Database of Genomic Variants usually are not reported. While NOT diagnostic, SNP data may allow 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 ROHs cover ≥5% of autosomal genome.
For the 5-cell chromosome analysis, a minimum of 5 metaphase cells are analyzed and 3 karyotypes are prepared at ≥400-450 band level.
Regardless of the specific testing option selected, prenatal testing of a CVS specimen includes FISH aneuploidies screen.
Limitations
SNP CMA may reveal whole genome mosaicism suggestive of presence of two different genomes, as in the case of maternal cell contamination. The presence of maternal cell contamination may limit the interpretation of CMA results. For products of conception, placenta or chorionic villi sample, when a single female genome is detected, it is assumed to represent the female fetus. However, the rare possibility that the DNA analyzed is maternal in origin cannot be excluded.
CMA will not detect balanced rearrangements (i.e., inversions, translocations), heterodisomy, or 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.
The karyotype analysis will not detect subtle chromosomal rearrangements. The 5-cell chromosome analysis will not adequately detect possible mosaicism.
Sample must be accompanied by a completed Test Request Form and Waiver for Microarray testing. Indicate the specific prenatal chromosomal microarray option. Include all pertinent medical and family history and/or a completed Prenatal Chromosomal Microarray Clinical Information Form.
鈥婭nterpretation Services
Detailed written report provided with genetic counseling phone consultation available to healthcare providers.
Follow-up Testing
麻豆传媒高清 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.
References
American College of Obstetricians and Gynecologists. Committee Opinion No. 581: The use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 122:1374–7, 2013.
Kearney HM, et al. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 13:680-5, 2011.
South ST, et al. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med. 15:901-9, 2013.
Wapner RJ, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 367:2175-84, 2012.
Reddy UM, et al., Karyotype versus Microarray Testing for Genetic Abnormalities after Stillbirth. The New England Journal of Medicine 367:23:2185-2193, 2013.
South ST, et al. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med. 15:901-9, 2013.
鈥婣mniotic fluid alpha-fetoprotein (AF-AFP) testing at 15-30 weeks gestation screens a fetus for an increased risk of open neural tube or open body wall defects. AF-AFP analysis can be used to further evaluate abnormal serum AFP levels identified during maternal serum screening.
AF-AFP testing is performed by the Associated Regional University Pathologists, Inc. (ARUP).
Acetylcholinesterase (AChE) testing is performed as a reflex confirmation test on individuals with an abnormal amniotic fluid alpha-fetoprotein (AF-AFP) level of 2.0 multiples of the mean (MOM) or greater.
Results and interpretation of the AChE are provided to the 麻豆传媒高清 Genetics Laboratory by Associated Regional University Pathologists, Inc. (ARUP) and the Foundation for Blood Research (FBR).
When maternal cell contamination (MCC) is not excluded by other test results, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) recommend that MCC studies be performed to optimize interpretation of the primary study molecular and/or cytogenetic results.
MCC testing by short tandem repeat (STR) analysis is performed by 麻豆传媒高清 Molecular Correlates (CMOCO), a partner lab of 麻豆传媒高清 Genetics Laboratory (CGL).
When ordered, MCC is conducted as needed:
on appropriate specimens (if adequate prenatal specimen/DNA).
Along with the prenatal specimen, a maternal sample is required:
Maternal peripheral blood – 3 ml in a 4ml EDTA (purple/lavender top) tube
OR
Maternal buccal/mouth swab – contact CGL for designated collection kit.
For additional information, contact CGL Client Services at (303)724-5701.
References
Nagan N, Faulkner NE, Curtis C, Schrijver I. Laboratory guidelines for detection, interpretation and reporting of maternal cell contamination in prenatal analyses. J Mol Diagn. 2011; 13(1):7-11.
South ST, Lee C, Lamb AN, Higgins AW, Kearney HM, Working Group for the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med. 2013 Nov;15(11):901-9.
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