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Autosomal Dominant Progressive External Ophthalmoplegia via the POLG2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
POLG2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11597POLG281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Kym Bliven, PhD

Clinical Features and Genetics

Clinical Features

Autosomal dominant progressive external ophthalmoplegia (adPEO) is one of several possible clinical manifestations of the mitochondrial DNA (mtDNA) deletion disorders. The characteristic features of this disease include progressive external ophthalmoplegia (PEO) and ptosis. Additionally, patients may present with exercise intolerance and muscle pain, mild weakness of the facial and limb muscles, speech difficulties, impaired glucose tolerance, elevated serum creatine kinase, and/or cardiac conduction defects (Longley et al. 2006; Craig et al. 2012). Affected individuals may also have cytochrome c oxidase (COX)-deficient muscle fibers and multiple mtDNA deletions in skeletal muscle (Longley et al. 2006; Craig et al. 2012). The age at onset of POLG2-related adPEO ranges from infancy to late adulthood (Longley et al. 2006; Young et al. 2011). Patients with earlier disease onset develop a multisystem disorder with severe phenotypes that can include failure to thrive, hypotonia, liver disease, seizures, lactic acidosis, and delayed psychomotor development (Young et al. 2011).


POLG2 defects are a rare cause of adPEO (Longley et al. 2006; Walter et al. 2010). More frequently, defects in the catalytic subunit (POLG) of the DNA polymerase gamma are implicated in this disease. In addition to POLG and POLG2, pathogenic variants in C10orf2, SLC25A4, RRM2B, and DNA2 can also cause adPEO (Fratter et al. 2010; Ronchi et al. 2013). POLG2 spans 8 exons and encodes for a p55 homodimeric accessory subunit of the DNA polymerase gamma that plays a key role in mtDNA replication. Several missense changes, small deletions/insertions, and one large intragenic deletion have been reported for POLG2-related adPEO (Longley et al. 2006; Walter et al. 2010; Young et al. 2011; Wang et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

To date, fewer than twenty cases of POLG2-related adPEO have been reported. Although we cannot precisely estimate clinical sensitivity at this time, pathogenic variants in POLG2 appear to be a rare cause of adPEO.

Testing Strategy

This test provides full coverage of all coding exons of the POLG2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with clinical symptoms consistent with adPEO, especially when POLG, C10orf2, SLC25A4, RRM2B, and DNA2 are normal. Testing is also indicated for family members of patients who have known POLG2 mutations.


Official Gene Symbol OMIM ID
POLG2 604983
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Craig K. et al. 2012. Mitochondrion. 12: 313-9. PubMed ID: 22155748
  • Fratter C. et al. 2010. Neurology. 74:1619-26. PubMed ID: 20479361
  • Longley M.J. et al. 2006. American Journal of Human Genetics. 78:1026-34. PubMed ID: 16685652
  • Ronchi D. et al. 2013. American Journal of Human Genetics. 92: 293-300. PubMed ID: 23352259
  • Walter M.C. et al. 2010. Journal of Neurology. 257:1517-23. PubMed ID: 20405137
  • Wang J. et al. 2012. Molecular Genetics and Metabolism. 106:221-30. PubMed ID: 22494545
  • Young M.J. et al. 2011. Human Molecular Genetics. 20:3052-66. PubMed ID: 21555342


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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View Ordering Instructions

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2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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