Limb Girdle Muscular Dystrophy Type 2A via the CAPN3 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4567 | CAPN3 | 81406 | 81406,81479 | $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 calpainopathies are a heterogeneous group of skeletal muscle disorders caused by variants in the CAPN3 gene. Limb girdle muscular dystrophy type 2A (LGMD2A; OMIM 253600), possibly the most prevalent form of LGMD (Guglieri et al. Hum Mut 29:258-266, 2008), is associated with atrophy and weakness of proximal girdle muscles, scapular winging, elevated serum CK levels, and late in the course of the disease, contractures. Clinical severity, age of onset, and disease progression are highly variable (Sáenz et al. Brain 128:732-742, 2005). The severe phenotype (pelvofemoral LGMD) first affects the pelvic girdle, then the shoulder girdle. Age of onset can be in childhood or adulthood. Early onset is infrequent in the scapulohumeral form, and the disease course is variable. Finally, hyperCKemia is found in young, asymptomatic individuals preceding disease onset. In some individuals, eosinophilic myositis (EM) is the only presenting feature (Krahn et al. Ann Neurol 59:905-911, 2006). These patients most often present in the first decade of life with idiopathic EM, elevated serum CK, and peripheral hypereosinophilia. In a second cohort of patients, all of whom similarly presented with EM, CAPN3 variants were found in each (5/5), and proximal muscle weakness and elevated serum CK was subsequently noted (Krahn et al. Clin Genet 80:398-402, 2011). Further evidence that EM is an early sign of calpainopathy comes from a retrospective study of muscle biopsies from CAPN3 variant-positive patients in which inflammatory changes with eosinophils were found in 5/17 patients (Krahn et al. 2011).
Genetics
CAPN3-related disorders are inherited in an autosomal recessive manner. Over 80% of CAPN3 variants are found in less than half of the 24 exons (http://www.dmd.nl/). Nonsense, missense, small insertions and deletions, splice site variants, gross deletions have been reported. Calpain-3 protein analysis as a means to screen LGMD patients has been shown to be highly specific but of limited sensitivity (Fanin et al., Hum Mut 24:52-62, 2004; Groen et al., Brain 130:3237-3249, 2007).
Clinical Sensitivity - Sequencing with CNV PG-Select
In large study of North American LGMD patients, Moore et. al,. (J. Neuropathol. Exp. Neurol. 65:995-1003, 2006) made a diagnosis of calpainopathy in 12% of their cohort using a combined immuno and molecular approach. In patients with a diagnosis of LGMD2A based on clinical features the likelihood of finding two CAPN3 variants ranges from 50% to 83% (Todorova et al., Clin Genet 67:356-358, 2005; Krahn et al., Clin Genet 69:444-449, 2006).
Testing Strategy
This test provides full coverage of all coding exons of the CAPN3 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Individuals with clinical symptoms consistent with LGMD, absent calpain-3 on western blots, or idiopathic eosinophilic myositis. Initial clinical signs are often tiptoe walking, difficulty in running, and scapular winging. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CAPN3.
Individuals with clinical symptoms consistent with LGMD, absent calpain-3 on western blots, or idiopathic eosinophilic myositis. Initial clinical signs are often tiptoe walking, difficulty in running, and scapular winging. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CAPN3.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| CAPN3 | 114240 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Limb-Girdle Muscular Dystrophy, Type 2A | AR | 253600 |
Citations
- Fanin, M., et.al. (2004). "Molecular diagnosis in LGMD2A: mutation analysis or protein testing?." Hum Mutat 24(1): 52-62. PubMed ID: 15221789
- Groen, E. J., et.al. (2007). "Analysis of the UK diagnostic strategy for limb girdle muscular dystrophy 2A." Brain 130(Pt 12): 3237-49. PubMed ID: 18055493
- Guglieri, M., et.al. (2008). "Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients." Hum Mutat 29(2): 258-66. PubMed ID: 17994539
- Krahn et al. (2011). Clin Genet 80:398-402.
- Krahn, M., et.al. (2006). "CAPN3 mutations in patients with idiopathic eosinophilic myositis." Ann Neurol 59(6): 905-11. PubMed ID: 16607617
- Krahn, M., et.al. (2006). "Screening of the CAPN3 gene in patients with possible LGMD2A." Clin Genet 69(5): 444-9. PubMed ID: 16650086
- Moore SA, Shilling CJ, Westra S, Wall C, Wicklund MP, Stolle C, Brown CA, Michele DE, Piccolo F, Winder TL, Stence A, Barresi R, King N, King W, Florence J, Campbell KP, Fenichel GM, Stedman HH, Kissel JT, Griggs RC, Pandya S, Mathews KD, Pestronk A, Serrano C, Darvish D, Mendell JR. 2006. Limb-girdle muscular dystrophy in the United States. J Neuropathol Exp Neurol 65: 995-1003. PubMed ID: 17021404
- Sáenz A. et al. Brain 128: 732–42. PubMed ID: 15689361
- Todorova, A., et.al. (2005). "Novel mutations in the calpain 3 gene in Germany." Clin Genet 67(4): 356-8. PubMed ID: 15733273
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
Loading...
×
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.