Test Code: 4837

Chromosomal CGH Microarray: Prenatal testing
Test Code: 4837
Turnaround time: 2 weeks

CONDITION DESCRIPTION

What is CEN4GEN Chromosomal CGH Microarray: Prenatal testing ?
This test utilizes 60,000 (60K) oligonucleotides to achieve whole genome coverage at a 75 kilobase (kb) spacing. It additionally covers more than 400 targeted regions, including known recurrent microdeletion/microduplication syndromes, centromere and telomere regions and disease-causing genes.

Why choose this test ?
Since the 1970’s couples have presented for prenatal genetic testing to learn medical information about their unborn baby. Genetic imbalances such as chromosomal deletions and duplications have long been known to be the leading cause of intellectual disability, birth defects and developmental disorders. Traditional methods for prenatal testing consist of G-banded chromosome analysis, which yields low resolution structural analysis of the chromosomes. Unlike the traditional analysis, this test allows for objective high-definition copy number analysis using the most current methods and software. This test has been used in the pediatric population resulting in much greater detection of genetic imbalances leading to the disruption of normal development.

Couples choosing prenatal diagnosis for any reason now have the option of microarray analysis to optimize detection of submicroscopic genetic imbalances. These couples may be assured that utmost care and consideration is employed in the interpretation of the array. 

To reduce unnecessary parental concern during the testing process, we request parental blood or DNA to be submitted along with the fetal sample. This allows for determination of inheritance (de novo or inherited) for the clinical interpretation of fetal findings that are of uncertain significance without having to arrange for parental blood draws and thus, reduces the wait time for the final interpretation of an abnormal result.

Approximately 1.7% of women who have invasive prenatal testing due to advanced maternal age (AMA) or abnormal serum screening will have an abnormal chromosomal microarray finding that would be missed by traditional karyotype (ref 1). This statistic rises to 6.0% for those pregnancies with structural fetal anomalies identified by ultrasound (ref 1). In response to these new data, the American College of Obstetricians and Gynecologists (ACOG) issued a committee opinion on the use of chromosomal microarray analysis in prenatal diagnosis, which provided the following practice recommendations to replace those set in 2009 (ref 2):

This test is recommended for any patient undergoing an invasive diagnostic prenatal procedure because of the ultrasound indication of one or more major structural anomalies in the fetus.  This test replaces the need for fetal karyotype.  This test or karyotype can be offered in those patients undergoing invasive diagnostic prenatal testing if no structural fetal abnormalities are noted on ultrasound regardless of maternal age.  This test is recommended for products of conception in the case of intrauterine fetal demise or stillbirth.  Patients choosing this test should receive both pre-test and post-test genetic counseling.  Since most abnormalities detected by this test are not associated with AMA, the use of this test for prenatal diagnosis should not be restricted to women aged 35 years and older.

References:
1. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012; 367:2175–8.
2. ACOG Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol 2013 Dec; 122:1374–7.

INDICATIONS
This test is appropriate for any woman seeking prenatal detection of chromosomal imbalance. Common indications for prenatal diagnosis include:

  • Advanced maternal age
  • Abnormal maternal serum screen
  • Abnormal ultrasound
  • Family history of a genetic imbalance
  • Parental concern

Indications specific to the need for further testing by microarray:

  • Previous normal fetal karyotype
  • Previous abnormal fetal karyotype showing an imbalance (excluding aneuploidies)
    – For unbalanced rearrangements, microarray can be used to size the deletion or duplication, and identify the genes involved
  • Previous abnormal fetal karyotype showing an apparently balanced rearrangement
    – For apparently balanced rearrangements, microarray can be used to test for cryptic deletions/duplications at the breakpoints

METHODOLOGY

DNA isolated from the prenatal sample is hybridized to a custom array containing oligonucleotide probes across the genome to detect copy number imbalances. FISH analysis or another method, such as G-banding, is used to confirm any abnormal findings. (Additional information is also provided above.)

DETECTION AND REFERENCE RANGE

Detection
The detection of deletions and duplications of 400 kb or greater is expected to be very high. Detection is limited to gain of copy number (duplication), loss of copy number (deletion) or normal copy number. Deletions and duplications of 400 kb or greater are reported. Smaller deletions or duplications in regions of known microdeletion/microduplication syndromes or in clinically relevant genes will also be reported.

The clinical sensitivity for known microdeletion or microduplication syndromes is available in our detection rate chart. The clinical sensitivity for other disorders is dependent on the proportion of cases caused by deletions/duplications compared with other mutations not detectable by array analysis. Microarray analysis will not detect balanced translocations, balanced inversions, imbalances smaller than the resolution of this array, triploidy, point mutations. Low level mosaicism (usually less than 25%) may not be detected by array, however in some cases the array will detect mosaic cell lines that fail to grow in culture.

Reference Range
Consecutive abnormal oligonucleotide probes are used to identify regions of imbalance. Log2 ratios less than 0.32 are indicative of a deletion or loss of genetic material, while those greater than 0.26 are indicative of a duplication or gain of genetic material.

SPECIMEN REQUIREMENTS
Type: Parental specimen
A maternal blood sample is REQUIRED to rule out maternal cell contamination. It is also recommended to send a paternal blood sample to determine the parental inheritance of microarray findings of uncertain clinical significance. This reduces the wait time for the final interpretation of a prenatal result. Submit 5cc of maternal and paternal whole blood samples in EDTA tubes, or 20 to 60 ug of maternal and paternal DNA, together with only 1 prenatal specimen type below.

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample overnight at room temperature for receipt at CEN4GEN within 24 hours of collection.

Type: Chorionic Villi
Specimen Requirements:
5 to 10 ug of DNA in TE buffer.

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample overnight at room temperature for receipt at CEN4GEN within 24 hours of collection.

Type: Amniotic Fluid
Specimen Requirements:
5 to 10 ug of DNA in TE buffer.

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample overnight at room temperature for receipt at CEN4GEN within 24 hours of collection.

Type: Cord blood
Specimen Requirements:
5 to 10 ug of DNA in TE buffer.

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample overnight at room temperature for receipt at CEN4GEN within 24 hours of collection.