Osteopetrosis via the CA2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11121 CA2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11121CA281479 81479(x2) $890 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 backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Juan Dong, PhD, FACMG

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.

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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