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Autosomal Dominant Progressive External Ophthalmoplegia and Hypertrophic Cardiomyopathy with Mitochondrial Myopathy via the SLC25A4 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
SLC25A4 81404 81404,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8831SLC25A481404 81404,81479 $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 a mitochondrial disorder characterized by progressive external ophthalmoplegia and ptosis, with multiple mitochondrial DNA (mtDNA) deletions in skeletal muscle (Chinnery 2014; Kaukonen et al. 2000). SLC25A4-associated adPEO is an adult-onset disease. Patients may not develop generalized muscle weakness until the fifth decade of life (Kaukonen et al. 2000; Komaki et al. 2002). To date, only a few SLC25A4-linked adPEO families have been reported worldwide (Kaukonen et al. 2000; Komaki et al. 2002; Park et al. 2011).

Hypertrophic cardiomyopathy with mitochondrial myopathy is another SLC25A4-related disorder (Palmieri et al. 2005; Echaniz-Laguna et al. 2012; Strauss et al. 2013). This adult-onset, autosomal recessive disease is characterized by hypertrophic cardiomyopathy, myopathy with exercise intolerance, lactic acidosis, and multiple mtDNA deletions. Ophthalmoplegia is notably absent in these patients, although one patient with complete loss of the SLC25A4 transcript presented with congenital cataracts (Echaniz-Laguna et al. 2012). Significant clinical variability may exist among family members with this disorder, which might be linked to differences in mitochondrial DNA (mtDNA) haplogroups (Strauss et al. 2013).


SLC25A4 defects are a rare cause of adult-onset, autosomal dominant progressive external ophthalmoplegia (PEO) (Kaukonen et al. 2000; Fratter et al. 2010). In contrast, SLC25A4-related hypertrophic cardiomyopathy with mitochondrial myopathy is inherited in an autosomal recessive manner (Echaniz-Laguna et al. 2012; Körver-Keularts et al. 2015; Strauss et al. 2013).

SLC25A4, commonly referred to as ANT1, has 4 exons and encodes for the heart and muscle isoform of adenine nucleotide translocator 1 (ANT1), an ATP/ADP translocator that is thought to play a key role in mtDNA maintenance (Kaukonen et al. 2000). Pathogenic SLC25A4 variants include missense mutations (the majority), two small frameshifting deletions, and one splicing variant (Human Gene Mutation Database).

Defects in C10orf2, POLG, POLG2, RRM2B, and DNA2 may also cause adPEO (Fratter et al. 2010; Ronchi et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

SLC25A4 defects accounted for approximately 4% of familial adPEO cases in one Italian cohort (Lamantea et al. 2002). The clinical sensitivity for SLC25A4-associated hypertrophic cardiomyopathy with mitochondrial myopathy is difficult to estimate at this time, as pathogenic variants have been reported in fewer than 20 individuals (Echaniz-Laguna et al. 2012; Körver-Keularts et al. 2015; Palmieri et al. 2005; Strauss et al. 2013).

No gross deletions or insertions have been reported in the SLC25A4 gene to date (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the SLC25A4 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 include patients with adPEO, particularly when sequencing of the C10orf2, POLG, POLG2 and RRM2B genes has not revealed any probable causative variants. Candidates for this test may also include patients affected by hypertrophic cardiomyopathy with mitochondrial myopathy. Testing is indicated for family members of patients who have known pathogenic variants in SLC25A4. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC25A4.


Official Gene Symbol OMIM ID
SLC25A4 103220
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

POLG-Related Mitochondrial Disorders via the POLG Gene
Autosomal Dominant Progressive External Ophthalmoplegia and other C10orf2-Related Disorders via the TWNK/C10orf2 Gene
Comprehensive Cardiology Panel
Mitochondrial Genome Maintenance/Integrity Nuclear Genes Panel


  • Chinnery P.F. 2014. Mitochondrial Disorders Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301403
  • Echaniz-Laguna A. et al. 2012. Journal of Medical Genetics. 49:146-50. PubMed ID: 22187496
  • Fratter C. et al. 2010. Neurology. 74:1619-26. PubMed ID: 20479361
  • Human Gene Mutation Database (Bio-base).
  • Kaukonen J. et al. 2000. Science. 289:782-5. PubMed ID: 10926541
  • Komaki H. et al. 2002. Annals of Neurology. 51:625-8. PubMed ID: 12112115
  • Körver-Keularts I.M. et al. 2015. JIMD Reports. 22:39-45. PubMed ID: 25732997
  • Lamantea E. et al. 2002. Annals of Neurology. 52:211-9. PubMed ID: 12210792
  • Palmieri L. et al. 2005. Human Molecular Genetics. 14:3079-88. PubMed ID: 16155110
  • Park K.P. et al. 2011. Journal of Clinical Neurology. 7:25-30. PubMed ID: 21519523
  • Ronchi D. et al. 2013. American Journal of Human Genetics. 92:293-300. PubMed ID: 23352259
  • Strauss K.A. et al. 2013. Proceedings of the National Academy of Sciences of the United States of America. 110:3453-8. PubMed ID: 23401503


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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