Chronic Progressive External Ophthalmoplegia (CPEO/PEO) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10507 DGUOK 81405,81479 Order Options and Pricing
DNA2 81479,81479
MGME1 81479,81479
OPA1 81407,81406
POLG 81406,81479
POLG2 81479,81479
RNASEH1 81479,81479
RRM2B 81405,81479
SLC25A4 81404,81479
SPG7 81406,81405
TK2 81405,81479
TWNK 81404,81479
TYMP 81405,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10507Genes x (13)81479 81404, 81405, 81406, 81407, 81479 $930 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

The accumulation of multiple mtDNA deletions can be a sign of the cell’s inability to maintain mitochondrial genome integrity. Multiple mtDNA deletions are typically seen in the skeletal muscle of patients affected by adult-onset chronic progressive external ophthalmoplegia (weakness of the extraocular muscles, referred to as CPEO or PEO), a disorder that is often accompanied by ptosis, oropharyngeal weakness, and proximal limb weakness (DiMauro and Hirano. 2011. PubMed ID: 20301382). Onset typically ranges between 20-40 years of age (Viscomi and Zeviani. 2017. PubMed ID: 28324239). In contrast to many other mitochondrial diseases, isolated CPEO is a relatively mild phenotype.

When patients display additional, often more severe phenotypes beyond those of the isolated form, this may be referred to as chronic progressive external ophthalmoplegia plus (CPEO+/PEO+). Additional symptoms are often multi-systemic and can include ataxia, psychiatric symptoms, sensory axonal neuropathy, hearing loss and/or optic atrophy, among others (Sommerville et al. 2014. PubMed ID: 27858775; Hanisch et al. 2015. PubMed ID: 25143630). At this time, genotype-phenotype correlation for this spectrum of disease is poorly understood.

Muscle biopsies of patients affected with CPEO are distinguished by the presence of ragged red fibers, a characteristic finding under modified Gomori trichrome staining that is explained by the accumulation of abnormal mitochondria within the subsarcolemmal space (DiMauro and Hirano. 2011. PubMed ID: 20301382; Viscomi and Zeviani. 2017. PubMed ID: 28324239). Patients generally present with decreased activities of the respiratory chain complexes, a consequence of reduced mitochondrial genome integrity, and histochemical staining for cytochrome c oxidase (COX, complex IV) is also either decreased or absent (Viscomi and Zeviani. 2017. PubMed ID: 28324239).

Genetics

Chronic progressive external ophthalmoplegia (CPEO) can be caused by defects in one of a number of genes within the nuclear genome: DGUOK, DNA2, MGME1, OPA1, POLG, POLG2, RNASEH1, RRM2B, SLC25A4, SPG7, TK2, TWNK, or TYMP. Inheritance may be primarily autosomal dominant (POLG2, OPA1, DNA2, SLC25A4) or autosomal recessive (DGUOK, MGME1, RNASEH1, TK2, TYMP), while reports of both recessive and dominant inheritance have been documented for a subset of genes (POLG, RRM2B, TWNK, SPG7).

Please note that CPEO may also present in individuals who harbor de novo or maternally-inherited mtDNA deletions, or pathogenic single nucleotide variants in the mitochondrial genome (DiMauro and Hirano. 2011. PubMed ID: 20301382; Chinnery. 2014. PubMed ID: 20301403). Sequencing of the mitochondrial genome is not offered as part of this test, but could be considered in individuals who test negative for plausible causative variants in the nuclear genes associated with this disorder.

Clinical Sensitivity - Sequencing with CNV PGxome

Based on a 2014 literature review by Sommerville et al., POLG and TWNK are likely the most common nuclear-encoded genes known to be responsible for chronic progressive external ophthalmoplegia; at the time of publishing, 258 and 143 patients, respectively, had been reported (Sommerville et al. 2014. PubMed ID: 27858775). TYMP, RRM2B, OPA1, and SLC25A4 were found in 30-50 patients each, while SPG7, MGME1, TK2, POLG2, DGUOK, DNA2, and MPV17 were less common causes of disease (<13 individuals each).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome-based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Individuals who present with suspected autosomal dominant or autosomal recessive adult-onset chronic progressive external ophthalmoplegia are good candidates for this test.

Genes

Official Gene Symbol OMIM ID
DGUOK 601465
DNA2 601810
MGME1 615076
OPA1 605290
POLG 174763
POLG2 604983
RNASEH1 604123
RRM2B 604712
SLC25A4 103220
SPG7 602783
TK2 188250
TWNK 606075
TYMP 131222
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Behr Syndrome AR 210000
Dominant Hereditary Optic Atrophy AD 165500
Glaucoma, Normal Tension, Susceptibility To AD 606657
Mitochondrial DNA depletion syndrome 11 AR 615084
Mitochondrial DNA Depletion Syndrome 12 (Cardiomyopathic Type) AR 615418
Mitochondrial DNA Depletion Syndrome 12A (Cardiomyopathic Type) AD AD 617184
Mitochondrial DNA Depletion Syndrome 14 (Encephalocardiomyopathic Type) AR 616896
Mitochondrial DNA Depletion Syndrome 2 (Myopathic Type) AR 609560
Mitochondrial DNA Depletion Syndrome 4B, Mngie Type AR 613662
Mitochondrial DNA Depletion Syndrome 7 AR 271245
Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form, With Renal Tubulopathy AR 612075
Mitochondrial DNA-Depletion Syndrome 3, Hepatocerebral AR 251880
Mitochondrial Neurogastrointestinal Encephalomyopathy Syndrome AR 603041
Optic Atrophy Type 1 AD 125250
Perrault Syndrome 5 AR 616138
Portal hypertension, noncirrhotic AR 617068
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions 1 AD 157640
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions, Autosomal Dominant, 2 AD 609283
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions, Autosomal Dominant, 3 AD 609286
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions, Autosomal Dominant, 4 AD 610131
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions, Autosomal Dominant, 5 AD 613077
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6 AD 615156
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions, Autosomal Recessive AR 258450
Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Recessive 2 AR 616479
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 AR 617069
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 AR 617070
Progressive Sclerosing Poliodystrophy AR 203700
Seckel syndrome 8 AR 615807
Sensory Ataxic Neuropathy, Dysarthria, And Ophthalmoparesis AR 607459
Spastic Paraplegia 7 AD 607259

Related Test

Name
PGxome®

Citations

  • Chinnery. 2014. PubMed ID: 20301403
  • DiMauro and Hirano. 2011. PubMed ID: 20301382
  • Hanisch et al. 2015. PubMed ID: 25143630
  • Sommerville et al. 2014. PubMed ID: 27858775
  • Viscomi and Zeviani. 2017. PubMed ID: 28324239

Ordering/Specimens

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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