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Mitochondrial Complex I Deficiency via the NDUFA1 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
NDUFA1 81404 81404,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9127NDUFA181404 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.

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

Mitochondrial complex I (CI) deficiency is characterized by a primary deficiency of the first and largest oxidative phosphorylation complex (Fassone and Rahman 2012). Primary mitochondrial CI deficiency accounts for roughly one-third of all oxidative phosphorylation disorders and is the most frequently reported childhood-onset mitochondrial disease (Skladal et al. 2003; Scaglia et al. 2004).

The majority of CI-deficient patients present within the first year of life (Distelmaier et al. 2009). Respiratory infections, gastrointestinal disease, or long periods of fasting may trigger the initial symptoms of this disorder and stimulate additional episodes, leading to rapid deterioration of the patient’s condition. Similar to other OXPHOS disorders, recurrent lactic acidosis is a prevalent finding in patients with CI deficiency. Additional clinical symptoms, which can involve single or multiple organ systems, may be highly heterogeneous. The most common clinical presentations in patients with nuclear-encoded CI deficiency include Leigh/Leigh-like syndrome (LS/LLS), leukoencephalopathy with macrocephaly, fatal infantile lactic acidosis, hypertrophic cardiomyopathy, and hepatopathy with renal tubulopathy (Fassone and Rahman 2012; Distelmaier et al. 2009). LS is a severe, progressive encephalopathy characterized by psychomotor delay or regression, isolated or combined mitochondrial complex deficiencies, elevated levels of lactate in the blood and/or cerebral spinal fluid, bilateral symmetrical lesions in the brainstem and basal ganglia, and neurologic manifestations such as hypotonia or ataxia (Rahman and Thorburn 2015; Lake et al. 2015).

NDUFA1-associated mitochondrial CI deficiency has been associated with either Leigh-like syndrome or myoclonic epilepsy and developmental delay (Fernandez-Moreira et al. 2007; Uehara et al. 2014). Patients presented within the first year of life, and additional symptoms included hypotonia, nystagmus, choreoathetosis, and/or seizures. Heterozygous female carriers that were reported within these families were noted to be asymptomatic. 


The mitochondrial respiratory chain complex I (nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase) is composed of at least 45 structural subunits (Fassone and Rahman 2012). 38 of these subunits are encoded by nuclear DNA, and 7 (MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, and MT-ND6) are encoded by mitochondrial DNA. The resulting holoenzyme complex plays a critical role in redox-driven proton translocation, which ultimately results in synthesis of adenosine triphosphate (ATP). Due to the many structural and accessory subunits required to support the assembly and function of complex I, mitochondrial CI deficiency is a genetically heterogeneous disorder. At least 33 genes have been linked to this disease to date.

NDUFA1-associated mitochondrial complex I deficiency is inherited in an X-linked recessive pattern. NDUFA1 encodes for a subunit of the mitochondrial CI, and several pathogenic missense variants have been reported in this gene to date (Fassone and Rahman 2012; Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, due to the limited number of reported cases (<10), the clinical sensitivity of NDUFA1-related mitochondrial complex I deficiency is difficult to estimate. In one small cohort, Fernandez-Moreira et al. identified causative NDUFA1 variants in 2/26 patients with an isolated complex I deficiency (~7.7%) (Fernandez et al. 2007). Analytical sensitivity is likely to be high, however, as all causative variants reported to date are missense changes.

Testing Strategy

This test provides full coverage of all coding exons of the NDUFA1 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

NDUFA1 sequencing should be considered for patients who present with symptoms consistent with mitochondrial complex I (CI) deficiency or for individuals with a family history of mitochondrial CI deficiency. We will also sequence the NDUFA1 gene to determine carrier status. 


Official Gene Symbol OMIM ID
NDUFA1 300078
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Mitochondrial Complex I Deficiency XL 252010

Related Test

Mitochondrial Complex I Deficiency Panel (Nuclear Genes)


  • Distelmaier F. et al. 2009. Brain. 132:833-42. PubMed ID: 19336460
  • Fassone and Rahman. 2012. PubMed ID: 22972949
  • Fernandez-Moreira D. et al. 2007. Annals of Neurology. 61:73-83. PubMed ID: 17262856
  • Human Gene Mutation Database (Bio-base).
  • Lake et al. 2015. PubMed ID: 25978847
  • Rahman and Thorburn. 2015. PubMed ID: 26425749
  • Scaglia et al. 2004. PubMed ID: 15466086
  • Skladal et al. 2003. PubMed ID: 12805096
  • Uehara N. et al. 2014. Annals of Clinical and Translational Neurology. 1:361-9. PubMed ID: 25356405


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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