Leigh Syndrome Associated With Mitochondrial Complex I Deficiency via the NDUFAF2 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
10027 NDUFAF2 81404 81404,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10027NDUFAF281404 81404, 81479 $890 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.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing 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.


Genetic Counselors


Clinical Features and Genetics

Clinical Features

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

NDUFAF2-associated mitochondrial CI deficiency has been reported in fewer than 20 patients to date. The most common clinical presentation is Leigh or Leigh-like syndrome (LS or LLS). LS is a severe, progressive encephalopathy characterized by a distinct set of diagnostic criteria, which include 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; Hoefs et al. 2009). LLS, which describes a similar clinical presentation in which one or more of these diagnostic characteristics is atypical, is frequently reported in patients with pathogenic variants in NDUFAF2 (Herzer et al. 2010). In particular, lactate elevation has been reported to be sporadic or absent in some patients, and neuroradiological presentations may be atypical (Barghuti et al. 2008; Ogilvie et al. 2005).


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 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; Sazanov 2015). 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 (Fassone and Rahman 2012).

NDUFAF2-associated mitochondrial complex I deficiency is inherited in an autosomal recessive pattern. NDUFAF2, also referred to as NDUFA12L in the literature, encodes for a molecular chaperone essential to mitochondrial complex I assembly (Ogilvie et al. 2005). Approximately ten causative variants have been reported in this gene to date. The majority of these variants are nonsense changes, although one missense variant has also been described, in addition to several small and gross deletions (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, due to the limited number of reported cases (<20), the clinical sensitivity of NDUFAF2-related mitochondrial complex I deficiency is difficult to predict. Rahman et al. estimate that <5% of reported autosomal recessive Leigh syndrome cases are caused by defects in NDUFAF2 (Rahman et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the NDUFAF2 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.

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

NDUFAF2 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 NDUFAF2 gene to determine carrier status.


Official Gene Symbol OMIM ID
NDUFAF2 609653
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Leigh Syndrome XL 256000
Mitochondrial Complex I Deficiency XL 252010

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  • Barghuti F. et al. 2008. Molecular Genetics and Metabolism. 94:78-82. PubMed ID: 18180188
  • Fassone E, Rahman S. 2012. Journal of Medical Genetics. 49:578-90. PubMed ID: 22972949
  • Herzer M. et al. 2010. Neuropediatrics. 41:30-4. PubMed ID: 20571988
  • Hoefs S.J. et al. 2009. Human Mutation. 30: E728-36. PubMed ID: 19384974
  • Lake N.J. et al. 2015. Journal of Neuropathy & Experimental Neurology. 74:482-92. PubMed ID: 25978847
  • Ogilvie I. et al. 2005. Journal of Clinical Investigation. 115:2784-92. PubMed ID: 16200211
  • 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
  • Sazanov L.A. et al. 2015. Nature Reviews Molecular Cellular Biology. 16:375-88. PubMed ID: 25991374
  • Scaglia et al. 2004. PubMed ID: 15466086
  • Skladal et al. 2003. PubMed ID: 12805096


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.
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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

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