Prenatal Testing and Guidelines

PreventionGenetics offers prenatal testing for samples collected from an ongoing pregnancy (please see postnatal test requirements for a sample collected from a POC). Given the delicate nature of genetic testing in this context, we will only accept the following indications for testing:

  • Fetal anomaly identified through abnormal prenatal screening, testing, or ultrasound findings
  • Known familial variant(s) classified as a VUS or higher
  • For CMA orders: advanced maternal age (AMA), high-risk NIPS or maternal serum screening result, or when invasive fetal testing is or has already been performed

Please be aware that we will not perform fetal testing for the indications of absence of heterozygosity (AOH), advanced paternal age (APA), family history in the absence of a known familial variant, or parental anxiety.

We strongly encourage you to contact our client services team to make them aware of your intended testing strategy before sample submission, and review our testing requirements below:

Test Requisition Form

Ordering Checklist

Note, testing will not be initiated until all requirements are met and all required samples received.

Prenatal Targeted (#990) Prenatal Gene Panel Sequencing Prenatal WES Prenatal CMA
Prenatal TRF ✔ ✔ ✔ Prenatal WES requisition STRONGLY preferred ✔
Signed HCP Form ✔ ✔ ✔ ✔
Indication of Fetal Anomaly ✔ (ROH/AOH, family history, parental anxiety are not accepted.) ✔ (ROH/AOH, family history, parental anxiety are not accepted.) ✔
Prenatal Sample ✔ ✔ ✔ ✔
Parental Sample ✔ ✔ ✔ ✔
Positive Control(s) ✔ (Must be relative to fetus.) ✔ (When family history is endorsed.)
Fetal Cell Cultures ✔ ✔

Prenatal testing is run STAT by default. Please indicate if testing should be run at a standard priority when placing your order. The average TAT provided in the test options below reflect the STAT time frame.

Note: Prenatal CMA and cell cultures cannot be canceled once a sample is received. In general, once a sample is sequenced and we have data on the patient in our system, we are unable to offer test cancellations. If you need to cancel a test that has not advanced in the testing process, please contact our client services department. Testing placed on hold will extend overall TAT. Testing placed on hold within 48 hours of receipt is eligible for cancellation.

Familial Variant Testing
TEST CODE 990

See our Targeted Testing page for additional test details and ordering.

Accepted Indications

  • There is a known familial variant classified internally as VUS, likely pathogenic, or pathogenic in a first-degree relative of the fetus

A clinical or biochemical diagnosis of genetic disease is not an accepted indication for testing, and familial variants must be known in advance and confirmed at PreventionGenetics. When needed, we recommend ordering family member testing STAT to ensure an expedited analysis.

Testing requirements

  • Fetal sample
  • Parental sample (preferably maternal for MCC studies)
  • Positive control sample(s)
  • Completed Prenatal Test Requisition Form with signed Healthcare Provider (HCP) Statement

Testing Recommendations

  • Maintenance of back-up cell culture
Average TAT - 2 weeks

Included In the Test Code

  • Targeted fetal analysis of up to 3 variants
  • Parental and/or proband report for SNVs

Assay (see Test Methods for more details)

The test method offering the highest sensitivity for capturing a variant of interest will be utilized. This may include:

  • Single-exon Sanger
  • Gene-centric aCGH
  • Long-range PCR and Bidirectional Sanger
  • CMA
  • Repeat Primed PCR (available for Huntington disease only)

Of note, MLPA is not validated for performance on fetal samples and will not be available.

CNV Analysis via Chromosomal Microarray (CMA)
SEE DEL/DUP ARRAY TESTS

We will perform CMA - Rapid Prenatal for ongoing pregnancies. See our full Test Descriptions for additional test details and limitations.

Accepted Indications

  • Advanced maternal age (AMA)
  • Abnormal fetal ultrasound findings
  • High-risk result on NIPS
  • Abnormal maternal serum screening
  • Family history of microdeletion, -duplication, balanced, or unbalanced translocation
  • When invasive prenatal testing is or has already been performed

Testing Requirements

  • Fetal sample
  • Parental sample (preferably maternal for MCC studies)
  • Indication for testing
  • Completed Prenatal Test Requisition Form with signed Healthcare Provider (HCP) Statement

Testing Recommendations

  • Please call client services to discuss the case and prepare the lab for sample arrival
Average TAT - 1 week

Included In the Test Code

  • Full CMA analysis of proband
  • Setup and maintenance of fetal cell cultures

Assay (see Test Methods for more details)

CMA via aCGH compares a patient's genomic DNA with a gender-matched reference genomic DNA to detect small copy number gains (duplications) and losses (deletions) on all 46 chromosomes in a single test. Allele Diagnostics' custom Agilent 180K CGH+SNP microarray contains ~107,000 distinct CGH probes distributed across the entire genome with a resolution of 20 kb in targeted regions and 80 kb in the backbone, and ~60,000 SNP probes resulting in ~5-10 Mb resolution for LOH detection.

Limitations: CMA cannot detect balanced chromosomal rearrangements such as inversions, balanced insertions, and reciprocal translocations, CNVs in regions not represented on the array, low levels of mosaicism, point mutations and indels, complete uniparental heterdisomy for the entire chromosome, imbalances in the mitochondrial genome, or imbalances when mosaicism for reciprocal CNVs exist.

Prenatal PGxome
SEE PRENATAL PGXOME TEST DESCRIPTION

We will perform WES for ongoing pregnancies when there is an indication (usually ultrasound or other) of a fetal anomaly. See our full Test Description for additional test details and limitations. PGxome tests for ongoing pregnancies require cultured cells.

Accepted Indications

  • Abnormal fetal ultrasound findings

Testing Requirements

  • Fetal sample
  • Parental sample (preferably maternal for MCC studies)
  • For Duo/Trio analyses: comparator sample(s) - testing cannot be initiated until these are received 
  • Indication for testing and detailed clinical notes
  • Maintenance of a back-up cell culture
  • Completed Prenatal Test Requisition Form with signed Healthcare Provider Statement

Testing Recommendations

  • Please call client services to discuss the case and prepare the lab for sample arrival
Average TAT - 2 weeks

Included In the Test Code

  • Full WES analysis of proband and comparator(s)
  • Two secondary findings opt-in categories

Assay (see Test Methods for more details)

PGxome uses Next Generation Sequencing (NGS) technologies to cover the coding regions of targeted genes plus ~10 bases of non-coding DNA flanking each exon. The following quality control metrics are generally achieved: >97% of target bases are covered at >20x, and mean coverage of target bases >100x.

Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All reported CNVs are confirmed using another technology such as aCGH, MLPA, or PCR.

NextGen Sequencing
SEE PRENATAL PRICES LISTED ON OUR WEBSITE

We will perform NextGen sequencing (NGS) tests for ongoing pregnancies when there is an indication (usually ultrasound or other) of a fetal anomaly. See our test-specific descriptions for additional test details and limitations. NGS tests for ongoing pregnancies require cultured cells.

Accepted Indications

  • Abnormal fetal ultrasound findings consistent with disorders tested for on the panel
  • Abnormal fetal test results (excluding ROH/AOH)
  • Fetus is an obligate carrier for a recessive condition because one biological parent is affected

Testing Requirements

  • Fetal sample
  • Parental sample (preferably maternal for MCC studies)
  • For Duo/Trio analyses: comparator sample(s)
  • Indication for testing that is consistent with the gene(s) of interest
  • Maintenance of a back-up cell culture
  • Completed Prenatal Test Requisition Form with signed Healthcare Provider Statement

Testing Recommendations

  • Please call client services to discuss the case and prepare the lab for sample arrival
Average TAT - 2 weeks

Included In the Test Code

  • Full NGS analysis of proband and comparator(s)
  • Fetal testing only

Assay (see Test Methods for more details)

Next Generation Sequencing (NGS) run on either PG-Select or WES probes covers the coding regions of targeted genes plus ~10 bases of non-coding DNA flanking each exon. The following quality control metrics are generally achieved: >97% of target bases are covered at >20x, and mean coverage of target bases >100x.

Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All reported CNVs are confirmed using another technology such as aCGH, MLPA, or PCR.

Full Gene Sanger Sequencing
SEE PRENATAL PRICES LISTED ON OUR WEBSITE

We will perform full gene Sanger sequencing tests for ongoing pregnancies when there is an indication (usually ultrasound or other indication) of fetal anomaly. See our test-specific descriptions for additional test details and limitations.

Accepted Indications

  • Abnormal fetal ultrasound findings consistent with disorders tested for on the panel
  • Abnormal fetal test results
  • Fetus is an obligate carrier for a recessive condition caused by variants in a paralogous gene because one biological parent is affected

Testing Requirements

  • Fetal sample
  • Parental sample (preferably maternal for MCC studies)
  • Indication for testing consistent with the gene(s) of interest
  • Completed Prenatal Test Requisition Form with signed Healthcare Provider Statement

Testing Recommendations

  • Please call client services to discuss the case and prepare the lab for sample arrival
  • Maintenance of back-up cell culture
Average TAT - 2 weeks

Included In the Test Code

  • Full gene Sanger analysis of the fetal sample

Assay (see Test Methods for more details)

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

CNV Analysis via Gene-Centric aCGH Test
SEE PRENATAL PRICES LISTED ON OUR WEBSITE

We will perform gene-centric aCGH for prenatal specimens when there is an indication (usually ultrasound or other) of a fetal anomaly. At this time MLPA is not validated for prenatal specimen types. Please contact our Genetic Counseling Team to discuss any familial CNV situations. See our full Test Description for additional test details and limitations.

Accepted Indications

  • Abnormal fetal ultrasound findings
  • Abnormal fetal test results

Testing Requirements

  • Fetal sample
  • Parental sample (preferably maternal for MCC studies)
  • Indication for testing consistent with the gene(s) of interest
  • Completed Prenatal Test Requisition Form with signed Healthcare Provider Statement

Testing Recommendations

  • Please call client services to discuss the case and prepare the lab for sample arrival
  • Maintenance of back-up cell culture
Average TAT - 2 weeks

Included In the Test Code

  • Fetal testing only

Assay (see Test Methods for more details)

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are analyzed.

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

Accepted Specimens