Leigh Syndrome Associated with Mitochondrial Complex I Deficiency via the NDUFA9 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
8207 NDUFA9 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8207NDUFA981479 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

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).

NDUFA9-associated isolated mitochondrial CI deficiency has been reported in only one patient to date (van den Bosch et al. 2012). The affected individual presented with neonatal-onset Leigh syndrome (LS) accompanied by profound hearing loss and retinitis pigmentosa. 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; van den Bosch et al. 2012).

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).

The NDUFA9 gene encodes for a structural subunit of the mitochondrial complex I, and NDUFA9-associated mitochondrial complex I deficiency is inherited in an autosomal recessive manner. Only one causative variant, a missense change, has been reported in this gene (van den Bosch et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, due to the limited number of reported cases, the clinical sensitivity of NDUFA9-related mitochondrial complex I deficiency is difficult to estimate. The single reported pathogenic variant is detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the NDUFA9 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

NDUFA9 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 NDUFA9 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
NDUFA9 603834
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Leigh Syndrome AR 256000

Related Tests

Name
NDUFA2-Related Leigh Syndrome (LS) via the NDUFA2 Gene
SURF1-Related Leigh Syndrome (LS) via the SURF1 Gene
Comprehensive Cardiology Panel
Leigh Syndrome Associated with Isolated Complex I Deficiency via the NDUFA12 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 Panel (Nuclear Genes)
Mitochondrial Complex I Deficiency via the NDUFA11 Gene
Mitochondrial Complex I Deficiency via the NDUFAF4 Gene
Mitochondrial Complex I Deficiency via the NDUFB3 Gene
Mitochondrial Complex I Deficiency via the NDUFB9 Gene
Mitochondrial Complex I Deficiency via the NDUFS4 Gene
Mitochondrial Complex I Deficiency via the NDUFV1 Gene
Mitochondrial Complex III Deficiency Panel (Nuclear Genes)
Mitochondrial Complex IV Deficiency via the COX15 Gene

Citations

  • Fassone and Rahman. 2012. PubMed ID: 22972949
  • Lake et al. 2015. PubMed ID: 25978847
  • Rahman and Thorburn. 2015. 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
  • van den Bosch B.J. et al. 2012. Journal of Medical Genetics. 49:10-5. PubMed ID: 22114105

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.

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

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

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.

Total Price: $
×
Copy Text to Clipboard
×