Mitochondrial Complex III Deficiency via the UQCC3 Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
9197 | UQCC3 | 81479 | 81479,81479 | $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.
Clinical Features and Genetics
Clinical Features
Mitochondrial complex III (CIII) deficiency is characterized by a deficiency of the third oxidative phosphorylation complex, also referred to as the cytochrome bc1 complex (Fernández-Vizarra and Zeviani 2015). In one cohort, isolated mitochondrial CIII deficiency accounted for approximately 5% of all oxidative phosphorylation (OXPHOS) disorders (Skladal et al. 2003).
The majority of CIII deficient patients manifest symptoms within the first year of life, although significant clinical and genetic heterogeneity may be observed among affected individuals. Similar to other OXPHOS disorders, recurrent lactic acidosis is a prevalent finding in patients with CIII deficiency, particularly during infections. Additional clinical features may include severe psychomotor delay or impairment, ataxia, muscle weakness, respiratory insufficiency, encephalomyopathy, and/or hypoglycemia (Fernández-Vizarra and Zeviani 2015; Dallabona et al. 2016; Ardissone et al. 2015). A subset of CIII deficient patients are diagnosed with Leigh syndrome, a subacute necrotizing encephalopathy characterized by elevated levels of lactate in blood and cerebral spinal fluid; bilateral symmetric necrotic lesions in the basal ganglia, brain stem, thalamus, and/or spinal cord; psychomotor delay or regression; and neurologic manifestations such as hypotonia or ataxia (Atwal 2014; Barel et al. 2008).
UQCC3-associated mitochondrial CIII deficiency has been identified in only one family to date (Wanschers et al. 2014). The affected child from this family presented at birth with severe lactic acidosis, hypoglycemia, hypotonia, and psychomotor delay. Several additional episodes of severe lactic acidosis occurred during infections.
Genetics
The mitochondrial respiratory chain complex III (CIII) is composed of 10 nuclear-encoded subunits and one mitochondrial-encoded subunit (MT-CYB), while several additional nuclear-encoded proteins are required for complex assembly (Fernández-Vizarra and Zeviani 2015). 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 the third complex, mitochondrial CIII deficiency is a genetically heterogeneous disorder, and at least 10 genes have been linked to this disease to date. Depending on the cellular localization of the affected gene, this disorder may have an autosomal recessive or maternal mode of inheritance. Causative variants in the nuclear genes (BCS1L, CYC1, LYRM7, TTC19, UQCC2, UQCC3, UQCRB, UQCRC2, and UQCRQ) are inherited in an autosomal recessive manner. In contrast, causative variants in the MT-CYB gene, which is encoded by the mitochondrial genome, are inherited in a maternal manner.
The UQCC3 gene, previously known as C11orf83, encodes for an assembly factor of the mitochondrial CIII. The UQCC3 protein may also be involved in stabilization of the III2/IV supercomplex (Desmurs et al. 2015). Only one causative variant, a homozygous missense change, has been reported in this gene to date (Wanschers et al. 2014).
Clinical Sensitivity - Sequencing with CNV PGxome
At this time, due to the limited number of reported cases, the clinical sensitivity of UQCC3-related mitochondrial complex III deficiency is difficult to estimate. The only reported pathogenic missense variant in this gene is detectable by sequencing.
Testing Strategy
This test provides full coverage of all coding exons of the UQCC3 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
Candidates for this test include patients with a deficiency of mitochondrial complex III, or those who present with symptoms consistent with complex III deficiency. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in UQCC3.
Candidates for this test include patients with a deficiency of mitochondrial complex III, or those who present with symptoms consistent with complex III deficiency. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in UQCC3.
Gene
Official Gene Symbol | OMIM ID |
---|---|
UQCC3 | 616097 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Mitochondrial Complex III Deficiency, Nuclear Type 9 | AR | 616111 |
Related Tests
Citations
- Ardissone A. et al. 2015. JIMD Reports. 22:115-20. PubMed ID: 25772319
- Atwal P.S. et al. 2014. JIMD Reports. 14:43-5. PubMed ID: 24368687
- Barel O. et al. 2008. American Journal of Human Genetics. 82:1211-6. PubMed ID: 18439546
- Dallabona C. et al. 2016. Brain. 139:782-94. PubMed ID: 26912632
- Desmurs M. et al. 2015. Molecular and Cellular Biology. 35:1139-56. PubMed ID: 25605331
- Fernández-Vizarra E., Zeviani M. 2015. Frontiers Genetics. 6:134. PubMed ID: 25914718
- Skladal D. et al. 2003. Clinical Pediatrics. 42:703-10. PubMed ID: 14601919
- Wanschers B.F. et al. 2014. Human Molecular Genetics. 23:6356-65. PubMed ID: 25008109
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
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.