BCS1L-Related Disorders (Mitochondrial Complex III Deficiency, GRACILE Syndrome, Björnstad Syndrome, and Leigh Syndrome) via the BCS1L Gene
Summary and Pricing
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture ProbesTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
7593 | BCS1L | 81405 | 81405,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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 deficiency is a disorder of oxidative phosphorylation (OXPHOS) that arises due to pathogenic variants in either one of the mitochondrial complex III subunits or one of the assembly proteins (including LYRM7, TTC19, and BCS1L) required to form the mature complex (Fernandez-Vizarra and Zeviani. 2015. PubMed ID: 25914718). BCS1L deficiency can result in a spectrum of disease that ranges from relatively mild (Björnstad syndrome) to severe (GRACILE or Leigh syndrome).
Björnstad syndrome is characterized by sensorineural hearing loss (nerve deafness) and pili torti (twisted hairs). Affected individuals generally develop hair loss within the first two years of life, and they may present with hearing loss within the first three to four years. Age of onset and clinical severity can be variable, however. Patients with Björnstad syndrome have also been reported to present with hypogonadism and/or intellectual disability (Selvaag. 2000. PubMed ID: 10694305; Hinson et al. 2007. PubMed ID: 17314340).
GRACILE syndrome (Growth Retardation, Amino aciduria, Cholestasis, Iron overload, Lactic acidosis, and Early death) is a neonatal metabolic disorder characterized by severe intrauterine growth retardation and fulminant lactic acidosis during the first days of life, followed by Fanconi-type amino aciduria and abnormalities in iron metabolism, including liver hemosiderosis (Fellman et al. 1998. PubMed ID: 9482441; Fellman et al. 2000. PubMed ID: 10654962). Affected infants fail to thrive, and often die neonatally or in early infancy.
Leigh syndrome is a subacute necrotizing encephalopathy characterized by elevated levels of lactate in blood or 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 (Rahman and Thorburn. 2015. PubMed ID: 26425749). Onset of this disorder usually occurs shortly after birth or within the first three years of life.
Genetics
Pathogenic variants in the BCS1L gene are inherited in an autosomal recessive manner. The BCS1L [BC1 (ubiquinol-cytochrome c reductase) synthesis-like] gene encodes for an assembly protein for complex III of the mitochondrial respiratory chain. Inactivation of BCS1L leads to disruption of complex III assembly, which in turn results in decreased activity of the mitochondrial respiratory chain and an increase in the production of reactive oxygen species (Hinson et al. 2007. PubMed ID: 17314340). Results from at least one study indicate that the levels of reactive oxygen species produced may be directly correlated with phenotypic severity (Hinson et al. 2007. PubMed ID: 17314340).
The majority of pathogenic variants described in this gene to date are missense; however, nonsense, splicing variants, and small frameshift deletions/insertions have also been reported (Human Gene Mutation Database). At least one BCS1L founder variant has been described in the Finnish population: c.232A>G (p.Ser78Gly) (Visapää et al. 2002. PubMed ID: 12215968).
Clinical Sensitivity - Sequencing with CNV PG-Select
At this time, due to the limited number of reported cases, the clinical sensitivity of BCS1L-related mitochondrial complex III deficiency is difficult to estimate. In one study carried out in Finland, twenty-one infants with a suspicion of mitochondrial disease had BCS1L gene sequencing; three infants harbored the known Finnish founder mutation (Fellman et al. 2008. PubMed ID: 18386115). All reported pathogenic variants in this gene are detectable by sequencing (Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the BCS1L gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this test include neonates who present with severe intrauterine growth retardation and fulminant lactic acidosis during the first days of life, and who later display Fanconi-type amino aciduria and abnormalities in iron metabolism, including liver hemosiderosis. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BCS1L.
Candidates for this test include neonates who present with severe intrauterine growth retardation and fulminant lactic acidosis during the first days of life, and who later display Fanconi-type amino aciduria and abnormalities in iron metabolism, including liver hemosiderosis. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BCS1L.
Gene
Official Gene Symbol | OMIM ID |
---|---|
BCS1L | 603647 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Name | Inheritance | OMIM ID |
---|---|---|
Bjornstad Syndrome | AR | 262000 |
GRACILE Syndrome | AR | 603358 |
Leigh Syndrome | AR, MT | 256000 |
Mitochondrial Complex III Deficiency | AR | 124000 |
Related Tests
Citations
- Fellman et al. 1998. PubMed ID: 9482441
- Fellman et al. 2000. PubMed ID: 10654962
- Fellman et al. 2008. PubMed ID: 18386115
- Fernandez-Vizarra and Zeviani. 2015. PubMed ID: 25914718
- Hinson et al. 2007. PubMed ID: 17314340
- Human Gene Mutation Database (Biobase).
- Rahman and Thorburn. 2015. PubMed ID: 26425749
- Selvaag. 2000. PubMed ID: 10694305
- Visapää et al. 2002. PubMed ID: 12215968
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
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.