French-Canadian type of Leigh syndrome via the LRPPRC 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 | |
---|---|---|---|---|---|
7737 | LRPPRC | 81479 | 81479,81479 | $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
The French-Canadian type of Leigh syndrome (LSFC; OMIM #220111), also called Saguenay-Lac-St-Jean cytochrome c oxidase deficiency (SLSJ-COX), is an infantile neurologic disorder characterized by acute severe lactic acidosis (Morin et al. Am J Hum Genet 53(2):488-496, 1993; Mootha et al. Proc Natl Acad Sci U S A 100(2):605-610, 2003; Debray et al. J Med Genet 48(3):183-189, 2011). Affected children have developmental delay of psychomotor skills, characteristic facial appearance, mental retardation, hypotonia, ataxia, and the development of lesions in the brainstem and basal ganglia. Approximately 90% of patients had metabolic and/or neurological acute crises and 82% of patients died at a median age of 1.6 years (Debray et al., 2011). This disease is clinically distinct from SURF1-caused Leigh syndrome and has been strictly found in patients from the Saguenay-Lac-St-Jean region, a genetic isolate in northern Québec, Canada.
Genetics
The French-Canadian type of Leigh syndrome is an autosomal recessive disorder caused by defects in the LRPPRC gene (Mootha et al., 2003; Debray et al., 2011). LRPPRC has 38 exons that encode a leucine-rich protein, which localizes primarily to mitochondria and may play a role in mRNA processing in both the nucleus and mitochondrion. So far, only two LRPPRC mutations have been reported to cause the disease: c.1061C>T (p.A354V), which accounted for all but one of pathogenic alleles; and c.3830_3839delins10 (p.C1277Xdel8). 55 of 56 patients were homozygous for c.1061C>T and the remaining patient was compound heterozygous for both mutations (Debray et al., 2011). The carrier frequency in the population of Saguenay-Lac-St-Jean is about 1 in 25 (De Braekeleer et al. Hum Hered 41(3):141-146, 1991; Morin et al., 1993).
Clinical Sensitivity - Sequencing with CNV PG-Select
So far, only two LRPPRC mutations have been reported to cause the disease: c.1061C>T (p.A354V), which accounted for all but one of pathogenic alleles; and c.3830_3839delins10 (p.C1277Xdel8). 55 of 56 patients were homozygous for c.1061C>T and the remaining patient was compound heterozygous for both mutations (Debray et al. J Med Genet 48(3):183-189, 2011).
Testing Strategy
This test provides full coverage of all coding exons of the LRPPRC 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 are patients with the French-Canadian type of Leigh syndrome. Testing is also indicated for family members of patients who have known LRPPRC mutations. Heterozygote screening for the c.1061C>T (p.A354V) mutation is now routinely performed in couples with Saguenay-Lac Saint-Jean ancestry (Debray et al., 2011). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LRPPRC.
Candidates for this test are patients with the French-Canadian type of Leigh syndrome. Testing is also indicated for family members of patients who have known LRPPRC mutations. Heterozygote screening for the c.1061C>T (p.A354V) mutation is now routinely performed in couples with Saguenay-Lac Saint-Jean ancestry (Debray et al., 2011). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LRPPRC.
Gene
Official Gene Symbol | OMIM ID |
---|---|
LRPPRC | 607544 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Leigh Syndrome, French Canadian Type | AR | 220111 |
Related Tests
Citations
- De Braekeleer, M. et al. (1991). “Hereditary disorders in Saguenay-Lac-St-Jean (Quebec, Canada).” Hum Hered 41(3):141-146. PubMed ID: 1937486
- Debray, F. et al. (2011.) “LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency.” J Med Genet 48(3):183-189. PubMed ID: 21266382
- Mootha, V. et al. (2003). “Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics.” Proc Natl Acad Sci U S A 100(2):605-610. PubMed ID: 12529507
- Morin, C. et al. (1993). "Clinical, metabolic, and genetic aspects of cytochrome C oxidase deficiency in Saguenay-Lac-Saint-Jean." Am J Hum Genet 53(2):488-496. PubMed ID: 8392291
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.