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Mitochondrial Complex I Deficiency via the NDUFB3 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
9129 NDUFB3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9129NDUFB381479 81479,81479 $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.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Kym Bliven, PhD

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).

NDUFB3-associated isolated mitochondrial CI deficiency has been reported in fewer than 20 patients to date (Haack et al. 2012; Calvo et al. 2012; Alston et al. 2016). All affected individuals presented with infantile-onset lactic acidosis, which was occasionally sporadic or associated with intercurrent illnesses. Hypotonia, developmental delays, encephalopathy, and/or hypertrophic cardiomyopathy were also identified in some patients (Haack et al. 2012; Alston et al. 2016). 

Genetics

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 shown to be involved in this disease to date (Fassone and Rahman 2012).

NDUFB3 encodes a structural subunit of the mitochondrial complex I, and NDUFB3-associated mitochondrial complex I deficiency is inherited in an autosomal recessive manner. Two causative variants (one missense and one nonsense variant) have been reported in this gene (Haack et al. 2012; Calvo et al. 2012; Human Gene Mutation Database). The pathogenic p.Trp22Arg variant was identified in eight different families of Irish descent, likely indicating a founder mutation (Alston et al. 2016). 

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, due to the limited number of reported cases, the clinical sensitivity of NDUFB3-related mitochondrial complex I deficiency is difficult to estimate. The few reported pathogenic variants are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the NDUFB3 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

NDUFB3 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 NDUFB3 gene to determine carrier status. 

Gene

Official Gene Symbol OMIM ID
NDUFB3 603839
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mitochondrial Complex I Deficiency AR 252010

Related Tests

Name
Leigh Syndrome Associated with Isolated Complex I Deficiency via the NDUFA12 Gene
Leigh Syndrome Associated with Mitochondrial Complex I Deficiency via the NDUFA9 Gene
Leigh Syndrome Associated With Mitochondrial Complex I Deficiency via the NDUFAF2 Gene
Leigh Syndrome Associated with Mitochondrial Complex I Deficiency via the NDUFS7 Gene
Mitochondrial Complex I Deficiency via the NDUFA11 Gene
Mitochondrial Complex I Deficiency via the NDUFAF4 Gene
Mitochondrial Complex I Deficiency via the NDUFB9 Gene
Mitochondrial Complex I Deficiency via the NDUFV1 Gene
Mitochondrial Complex I Deficiency via the NDUFV2 Gene

Citations

  • Alston C.L. et al. 2016. Journal of Medical Genetics. 53:634-41. PubMed ID: 27091925
  • Calvo S.E. et al. 2012. Science Translational Medicine. 4:118ra10. PubMed ID: 22277967
  • Fassone and Rahman. 2012. PubMed ID: 22972949
  • Haack T.B. et al. 2012. Journal of Medical Genetics. 49:277-83. PubMed ID: 22499348
  • Human Gene Mutation Database (Bio-base).
  • 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/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.
  • 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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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