Osteopetrosis via the CA2 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11121 | CA2 | 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.
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
Osteopetrosis (also called Marble bone disease) is a disorder of increased bone density and bone mass caused by malfunction of bone resorption. Affected patients are at high risk of frequent bone fractures, delayed healing, hip osteoarthritis and osteomyelitis. Some patients may have vision loss, hearing loss, and paralysis of facial muscles and bone marrow abnormalities caused by abnormal dense bone structure. Other features include short stature, development delay, dental abnormalities, hepatosplenomegaly, intellectual disability, and epilepsy (Tolar et al. 2004; Del Fattore et al. 2008; Sobacchi et al. 2013). Osteopetrosis is currently known to be caused by pathogenic variants in the following genes: CLCN7, LRP5, TCIRG1, TNFSF11, CA2, OSTM1, PLEKHM1, SNX10 and TNFRSF11A.
Genetics
Pathogenic variants in the CA2 gene can cause autosomal recessive osteopetrosis with renal tubular acidosis and cerebral calcification. The CA2 protein coded by the CA2 gene is an isozyme of carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide and stimulates the chloride-bicarbonate exchange activity. To date, nearly 30 unique pathogenic variants have been reported. They are: missense (22%), nonsense (11%), splicing (15%) and small deletion/duplication (52%). No large deletions/duplications have been reported (Hu et al. 1997; Shah et al. 2004; Human Gene Mutation Database). Nearly all patients of Arabic descent carry the splice c.232+1G>A (also called c.297+1 G>A) variant (Hu et al. 1997).
Clinical Sensitivity - Sequencing with CNV PGxome
CA2 pathogenic variants were identified in all 21 patients who had CA2 deficiency (Shah et al. 2004). No large deletions/duplications have been reported (Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the CA2 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 are patients with symptoms consistent with osteopetrosis with renal tubular acidosis and brain calcification and the family members of patients who have known CA2 pathogenic variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CA2.
Candidates for this test are patients with symptoms consistent with osteopetrosis with renal tubular acidosis and brain calcification and the family members of patients who have known CA2 pathogenic variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CA2.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| CA2 | 611492 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Osteopetrosis With Renal Tubular Acidosis | AR | 259730 |
Citations
- Del Fattore A. et al. 2008. Bone. 42: 19-29. PubMed ID: 17936098
- Hu PY, Lim EJ, Ciccolella J, Strisciuglio P, Sly WS. 1997. Seven novel mutations in carbonic anhydrase II deficiency syndrome identified by SSCP and direct sequencing analysis. Hum. Mutat. 9: 383–387. PubMed ID: 9143915
- Human Gene Mutation Database (Bio-base).
- Shah GN, Bonapace G, Hu PY, Strisciuglio P, Sly WS. 2004. Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): Novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. Hum. Mutat. 24: 272–272. PubMed ID: 15300855
- Sobacchi C, Schulz A, Coxon FP, Villa A, Helfrich MH. 2013. Osteopetrosis: genetics, treatment and new insights into osteoclast function. Nature Reviews Endocrinology 9: 522-536. PubMed ID: 23877423
- Tolar J. et al. 2004. New England Journal of Medicine. 351: 2839-49. PubMed ID: 15625335
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
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ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.