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Mitochondrial Complex IV Deficiency via the PET100 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7779 PET100 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7779PET10081479 81479,81479 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Kym Bliven, PhD

Clinical Features and Genetics

Clinical Features

Mitochondrial complex IV (CIV) deficiency is characterized by a deficiency of the fourth oxidative phosphorylation (OXPHOS) complex of the mitochondrial respiratory chain (Fassone and Rahman 2012). Primary mitochondrial CIV deficiency is estimated to account for approximately one-fifth of all OXPHOS disorders (Skladal et al. 2003; Scaglia et al. 2004).

The majority of CIV-deficient patients present with a severe, early-onset disease within the first year of life. Similar to other OXPHOS disorders, recurrent lactic acidosis is a prevalent finding in affected individuals. Patients may display significant heterogeneity in additional clinical features, which can include encephalopathy, hypertrophic cardiomyopathy, hypotonia, epilepsy, microcephaly, dystonia, psychomotor delay or impairment, nystagmus, respiratory insufficiency, ataxia, muscle weakness, and/or CIV-deficient Leigh or Leigh-like syndrome (Pecina et al. 2004; Darin et al. 2003; Alfadhel et al. 2011). Leigh syndrome (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).

PET100-related CIV deficiency has been reported in affected individuals of seven families to date; in six of these families, a shared founder mutation was identified (Lim et al. 2014; Oláhová et al. 2015). Affected individuals presented with either fatal neonatal lactic acidosis or a severe Leigh-like disease within the first year of life. Seizures were evident in all cases reported to date.

Genetics

The cytochrome c oxidase enzyme, also referred to as mitochondrial complex IV (CIV) or COX, is the terminal oxidase of the mitochondrial respiratory chain. Over 30 genes are involved in the structure, assembly, or function of this enzyme (Kadenbach and Hüttemann 2015). Primary mitochondrial CIV deficiency has been linked to pathogenic variants in approximately half of these genes to date. Three CIV subunits (MT-CO1, MT-CO2, and MT-CO3), which form the catalytic core of the enzyme, are encoded by the mitochondrial genome. Pathogenic variants in MT-CO1, MT-CO2, and MT-CO3 are maternally inherited (Rak et al. 2016). Defects in the remaining nuclear-encoded genes, including PET100, exhibit autosomal recessive inheritance.

The PET100 gene encodes for a CIV assembly factor (Lim et al. 2014). One missense variant and one nonsense variant have been reported in the PET100 gene to date (Human Gene Mutation Database). The missense variant, which results in the substitution of the initiation codon for an isoleucine, is a founder mutation that was identified in patients with Lebanese ancestry (Lim et al. 2014).

Clinical Sensitivity - Sequencing with CNV PG-Select

At this time, due to the limited number of reported cases and the absence of large cohort studies, the clinical sensitivity of PET100-related mitochondrial complex IV deficiency is difficult to estimate. Analytical sensitivity is expected to be high, as all reported variants to date may be identified via sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the PET100 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

PET100 sequencing could be considered for patients who present with symptoms consistent with mitochondrial complex IV (CIV) deficiency or for individuals with a family history of mitochondrial CIV deficiency, particularly if no causative variants were identified in the SURF1 gene. We will also sequence the PET100 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
PET100 614770
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mitochondrial Complex IV Deficiency AR 220110

Related Tests

Name
TACO1-Related Leigh Syndrome (LS) via the TACO1 Gene
Leigh and Leigh-Like Syndrome Panel (Nuclear Genes Only)
Mitochondrial Complex IV Deficiency via the COA3 Gene
Mitochondrial Complex IV Deficiency via the COA8/APOPT1 Gene
Mitochondrial Complex IV Deficiency via the COX14 Gene
Mitochondrial Complex IV Deficiency via the COX20 Gene
Mitochondrial Complex IV Deficiency via the COX6B1 Gene
Mitochondrial Complex IV Deficiency via the FASTKD2 Gene
Mitochondrial Complex IV Deficiency via the SCO1 Gene

Citations

  • Alfadhel et al. 2011. PubMed ID: 21412973
  • Darin et al. 2003. PubMed ID: 14681757
  • Fassone and Rahman. 2012. PubMed ID: 22972949
  • Human Gene Mutation Database (Bio-base).
  • Kadenbach and Hüttemann. 2015. PubMed ID: 26190566
  • Lake et al. 2015. PubMed ID: 25978847
  • Lim et al. 2014. PubMed ID: 24462369
  • Oláhová M. et al. 2015. European Journal of Human Genetics. 23:935-9. PubMed ID: 25293719
  • Pecina et al. 2004. PubMed ID: 15119951
  • Rahman S, Thorburn D. 2015. Nuclear Gene-Encoded Leigh Syndrome Overview. In: Pagon RA, Aadam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews (®), Seattle (WA): University of Washington, Seattle. PubMed ID: 26425749
  • Rak et al. 2016. PubMed ID: 26846578
  • 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

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

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STAT and Prenatal Test Options are not available with Patient Plus.

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