Skip to main content

PMS2 Del/Dup Testing by MLPA

Omics test Model
Test Code D5232
Test Summary

This assay detects copy number changes in the PMS2 gene, which is associated with Lynch syndrome.

Turn Around Time 12 days
Acceptable Sample Types DNA , Dried Blood Spots , Saliva , Whole Blood (EDTA)
Acceptable Billing Types Institutional Billing , Self (patient) Payment
NY Approved No
Self (patient) Price $1,600.00
Institutional Price $1,600.00
CPT Codes** 81319(x1)
*TAT starts after the sample and all required sample information is received at the processing laboratory.

**The CPT codes listed are in accordance with Current Procedural Terminology, a publication of the American Medical Association, and are provided for informational purposes only. CPT coding is the sole responsibility of the billing party.

This testing service has not been cleared or approved by the U.S. Food and Drug Administration. Testing services may not be licensed in accordance with the laws in all countries. The availability of specific test offerings is dependent upon laboratory location.

Test Description

Multiplex Ligation-Dependent Probe Amplification (MLPA) detects deletions and duplications of single and multiple exons within a given gene (PMID: 20938835). It is a semi-quantitative technique to determine relative copy number using a multiplex PCR-based reaction. Only hybridized and ligated adjacent probe oligonucleotides are amplified by PCR, thus specific for the sequence of interest. This test involves a copy number analysis of the PMS2 gene.

Indications for Testing

  • Diagnostic testing for Individuals with Lynch syndrome or a family history of Lynch syndrome
  • Familial testing for individuals with a family history of known copy number changes in the PMS2 gene

Condition Description

Lynch syndrome (LS, MIM# 120435; formerly known as HNPCC, Hereditary Nonpolyposis Colorectal Cancer) is the most common heritable colorectal carcinoma (CRC) syndrome and is responsible for 2% to 4% of all CRC cases in the Western world. Heterozygous germline mutations in one of the mismatch repair (MMR) genes MSH2 (MIM# 609309), MLH1 (MIM# 120436), MSH6 (MIM# 600678), or PMS2 (MIM# 600259) are responsible for Lynch syndrome (PMID: 20301390). Another cause of Lynch syndrome is the deletion of the 3’ part of EPCAM, leading to constitutional epigenetic silencing of the downstream MSH2 gene. The estimated contribution of the different genes to Lynch syndrome is 15-40% for MLH1, 20-40% for MSH2, 12-35% for MSH6, 5-25% for PMS2 and <10% for EPCAM (PMID: 20301390).

The PMS2 gene provides instructions for making a protein essential to repairing DNA. This protein helps fix errors made when DNA is copied (replication) in preparation for cell division. The PMS2 protein joins with MLH1 to form a protein complex, which coordinates the activities of other proteins that repair errors made during DNA replication. Genetic testing for mutations in PMS2 is greatly complicated by numerous unprocessed PMS2 pseudogenes and segmental duplications containing unspliced segments of the gene (PMID: 8586419). There are 14 pseudogenes containing exons 1 to 5 in various compositions on the long arm of chromosome 7, and one highly homologous copy (PMS2CL) encompassing the 3' end of PMS2, that is, exon 9 and exons 11 to 15, embedded in a 100 kb inverted duplicon, 700 kb centromeric of PMS2 on chromosomal 7p. Among the defects in the PMS2 gene are deletions and duplications of complete exons, which are usually missed by standard sequence analysis. The MLPA technique can detect most of these deletions and duplications except for CNV in the PMS2 exon 12-15 region and therefore complements sequence analysis of the PMS2 gene.



Test Methods and Limitations

MLPA-based assay for the detection of deletions/duplications in the PMS2 gene. The MRC-Holland reagent kits and the Applied Biosystem 3730xl DNA Analyzer instrument generate fragment analysis data.

Detailed Sample Requirements

Dried Blood Spots
Test Details Page
Collection Container(s) Dried blood spot card

Follow kit instructions. Briefly, allow blood to saturate the card until indicated areas are filled and blood has soaked through the card. Air dry the card at ambient temperature for at least 3 hours.

  • NBS: Please contact Revvity Omics to request the StepOne® kit.
  • Gene Sequencing: Please contact Revvity Omics to request the DBS collection kit.
  • For pre-punched DBS: The required minimum is 6 punches
Sample Condition Follow the instructions provided with the collection set. Store the dried blood at ambient temperature for up to two days. If the specimen cannot be sent as soon as it is dry, the filter paper should be placed in a sealable plastic bag and stored in a refrigerator (≤ 8°C) or preferably in a freezer.
Shipping Follow kit instructions. Double bag and ship overnight at ambient temperature.
DNA, Isolated
Test Details Page

Required DNA Quantity by Test Type*:

  • Next Generation Sequencing (NGS): Send >1000 ng total gDNA @ >15 ng/μL. Please ship samples in 10mM Tris. Do not use EDTA.
  • Sanger Sequencing: Send >500 ng total gDNA @ >15 ng/μL (varies by the size of the gene and the variants requested).
  • Non-Sanger Sequencing Tests: Send >500 ng total gDNA @ >15 ng/μL.
Sample Condition * Required DNA Quality: High molecular weight DNA (>12kb). A260/A280 reading should be ≥ 1.8. A260/230 a ratio range of 1.8 to 2.2. Contact the laboratory for specific amounts if total ng cannot be met.
Shipping Ship overnight at ambient temperature.
Special Sample Instructions
  • Research Laboratories: DNA extracted in research laboratories is not acceptable. Only under exceptional circumstances (e.g., proband not available) will DNA extracted in a research laboratory be accepted for clinical testing. Additional testing (e.g., of other family members) may be required to confirm results.
  • Laboratories outside the United States: Non-US laboratories are not subject to CLIA regulations and will be reviewed on a case-by-case basis. Please call to speak with a laboratory genetic counselor before submitting a DNA sample from any non-CLIA-certified laboratory.
  • Special Notes: If extracted DNA is submitted, information regarding the method used for extraction should be sent along with the sample.
Whole Blood (EDTA) (Preferred Sample)
Test Details Page
Collection Container(s) EDTA (purple top)
Collection Infants (< 2-years): 2 to 3 mL; Children (>2-years): 3 to 5 mL; Older children and adults: Minimum 5mL. The blood tube should be inverted several times immediately after blood collection to prevent coagulation.
Sample Condition Store at ambient temperature. Do not refrigerate or freeze.
Shipping Ship overnight at ambient temperature ensuring receipt within 5-days of collection.
Special Sample Instructions Clotted or hemolyzed samples are not accepted.
Test Details Page
Collection Container(s) Oragene™ Saliva Collection Kit or ORAcollect-Dx kit
Collection Collect saliva on an Oragene™ Saliva Collection Kit ORAcollect-Dx kit according to the manufacturer's instructions.
Sample Condition Store at ambient temperature. Do not refrigerate or freeze.
Shipping Ship overnight at ambient temperature.
Special Sample Instructions Please contact Revvity Omics to request the saliva collection kit for patients who cannot provide a blood sample as whole blood is the preferred sample. Testing using Saliva swabs is currently not available for customers in India. Contact the Revvity Omics laboratory for more information.