DNA icon

Mitochondrial Combined Oxidative Phosphorylation Deficiency via the MTFMT 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
MTFMT 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9929MTFMT81479 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.

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

Combined oxidative phosphorylation (OXPHOS) deficiency is a multi-systemic disorder characterized by reduced activity of two or more mitochondrial respiratory chain enzyme complexes. Combined OXPHOS deficiency accounts for roughly one-quarter to one-third of all oxidative phosphorylation disorders (Skladal et al. 2003; Scaglia et al. 2004).

Patients with MTFMT-associated oxidative phosphorylation deficiency generally present within the first year of life, although clinical presentation may range from mild (with survival into adulthood and eventual apparent clinical stability) to severe (resulting in death within the first few years of life). Although many MTFMT-deficient patients show combined oxidative phosphorylation defects in muscle tissue upon biochemical analysis, a subset of patients may present with an isolated complex I deficiency (Haack et al. 2014). Overall, affected individuals exhibit a primarily encephalomyopathic phenotype, with clinical symptoms such as lactic acidosis, hypotonia, microcephaly, developmental delays, cognitive impairment, optic atrophy, dysarthria, convulsions, ataxia and spasticity at later disease stages, stroke-like episodes, and/or acute respiratory insufficiency (Haack et al. 2014; Pena et al. 2016; Neeve et al. 2013; Tucker et al. 2011). In the majority of patients, MRI analysis often leads to a diagnosis of classical Leigh syndrome, a severe, progressive encephalopathy characterized by bilateral symmetrical lesions in the brainstem and basal ganglia; psychomotor delay or regression; isolated or combined mitochondrial complex deficiencies; elevated levels of lactate in the blood and/or cerebral spinal fluid; and neurologic manifestations such as hypotonia or ataxia (Haack et al. 2014; Rahman and Thorburn 2015; Lake et al. 2015).


Combined oxidative phosphorylation (OXPHOS) deficiency may be an autosomal recessive, X-linked, or maternally-inherited disease. Pathogenic variants in over 30 different nuclear and mitochondrial genes have been reported as causative for this disorder; the majority of these genes encode for components of the mitochondrial translation machinery.

Nuclear genes associated with autosomal recessive inheritance of combined OXPHOS deficiency include: AARS2, ATP5A1, BOLA3, C12orf65, EARS2, ELAC2, FARS2, GFER, GFM1, GTPBP3, ISCU, LYRM4, MARS2, MRPL3, MRPL44, MRPS16, MRPS22, MTFMT, MTO1, NARS2, NFU1, PARS2, PNPT1, PUS1, RMND1, SERAC1, SFXN4, TARS2, TRMT5, TSFM, TUFM, VARS2, and YARS2. AIFM1 is associated with X-linked recessive inheritance of this disease. Pathogenic defects in any of the mitochondrial-encoded tRNA genes (22 total) or rRNA genes (2 total) are expected to result in maternally-inherited combined oxidative phosphorylation deficiency (Smits et al. 2010).

Additionally, defects in the mitochondrial depletion/deletion syndrome genes (see Test #1399) or coenzyme Q10 deficiency genes (see Test #4529) may result in a combined OXPHOS deficiency in conjunction with coenzyme Q10 deficiency, quantitative mitochondrial genome depletion, or a large deletion(s) of the mitochondrial genome.

The MTFMT gene encodes for the mitochondrial methionyl-tRNA formyltransferase, responsible for formylation of the initiator Met-tRNA (Haack et al. 2014). Approximately 15 causative variants have been reported in this gene to date, including several missense and nonsense variants, one splicing variant, and several small deletions resulting in frameshifts (Human Gene Mutation Database). One particular missense change (p.Ser209Leu) appears to be prevalent among affected individuals (Haack et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

In a cohort of 350 patients who presented with a suspected mitochondrial disorder and either isolated or combined oxidative phosphorylation deficiencies, Haack and colleagues identified causative MTFMT variants in 4 patients (~1%) (Haack et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the MTFMT 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

MTFMT sequencing could be considered for patients who present with symptoms consistent with combined oxidative phosphorylation deficiency or for individuals with a family history of this disorder. We will also sequence the MTFMT gene to determine carrier status.


Official Gene Symbol OMIM ID
MTFMT 611766
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Combined Oxidative Phosphorylation Deficiency 15 AR 614947

Related Test

Mitochondrial Complex I Deficiency Panel (Nuclear Genes)


  • Haack T.B. et al. 2014. Molecular Genetics and Metabolism. 111:342-52. PubMed ID: 24461907
  • Human Gene Mutation Database (Bio-base).
  • Lake et al. 2015. PubMed ID: 25978847
  • Neeve V.C. et al. 2013. Mitochondrion. 13:743-8. PubMed ID: 23499752
  • Pena J.A. et al. 2016. Journal of Child Neurology. 31:215-9. PubMed ID: 26060307
  • Rahman S, Thorburn D. 2015. Nuclear Gene-Encoded Leigh Syndrome 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: 26425749
  • Scaglia et al. 2004. PubMed ID: 15466086
  • Skladal D. et al. 2003. Brain: A Journal of Neurology. 126:1905-12. PubMed ID: 12805096
  • Smits P. et al. 2010. Journal of Biomedicine and Biotechnology. 2010:737385. PubMed ID: 20396601
  • Tucker E.J. et al. 2011. Cell Metabolism. 14:428-34. PubMed ID: 21907147


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

loading Loading... ×


An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

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.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
Copy Text to Clipboard