Hereditary Multiple Osteochondromas (HMO) via the EXT2 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 | |
|---|---|---|---|---|---|
| 7091 | EXT2 | 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
Hereditary multiple osteochondromas, also known as hereditary multiple exostoses (OMIM#133700 for type I and #133701 for type II), are benign cartilage-capped bone tumors (exostoses) that grow outward from the metaphyses of long bones. Osteochondromas can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, premature osteoarthrosis, and compression of peripheral nerves (Schmale et al. GeneReviews. 2008). The lifetime risk for malignant osteochondrosarcoma is low (1-5%), but the risk increases with age (Vink et al. Eur J Hum Genet 13:470-474, 2005).
Genetics
HMO is inherited as an autosomal dominant trait with high penetrance (~95%). About 10% of affected individuals have HMO as the result of a de novo variant. Two genes (EXT1 and EXT2) are known to be associated with HMO. A possible third locus is thought to account for a small number of cases, but the gene has not yet been identified. Both EXT gene products (exostosin-1, exostosin-2) are involved in the biosynthesis of heparan sulfate. EXT1 and EXT2 encode glycosyltransferases that interact as heterooligomeric complexes and participates in cell signaling and chondrocyte proliferation and differentiation (McCormick et al. Proc Natl Acad Sci 97:668–673, 2000). EXT1 variants account for 56-78% of HMO cases, and EXT2 variants account for 21-44% of HMO cases (Schmale et al. GeneReviews 2008). In both genes, most of reported variants are nonsense, frameshift, and splice site variants. Individuals with EXT1 variants were found to have a greater number of exostoses, a greater incidence of limb malalignment with shorter limb segments and height, and more frequent pelvic and flat bone involvement than those with EXT2 variants (Alvarez et al. Clin Genet 70:122–130, 2006). The risk of chondrosarcoma may also be higher in individuals with an EXT1 variant (Porter et al. J Bone Joint Surg Br 86:1041–1046, 2004).
Clinical Sensitivity - Sequencing with CNV PG-Select
Disease variants in EXT1 and EXT2 are predicted to be detected in 70-85% of affected individuals with HMO (Schmale et al. GeneReviews 2008).
Large deletions may be found in up to 10% of patients with HMO (Vink et al. Eur J Hum Genet 13:470-474, 2005).
Testing Strategy
This test provides full coverage of all coding exons of the EXT2 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 clinical and radiographic features consistent with HMO and family members of patients who have known EXT2 variants.
Candidates for this test are patients with clinical and radiographic features consistent with HMO and family members of patients who have known EXT2 variants.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| EXT2 | 608210 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Exostoses, Multiple, Type II | AD | 133701 |
Related Test
| Name |
|---|
| Hereditary Multiple Osteochondromas (HMO) Panel |
Citations
- Alvarez, C., et.al. (2006). "The genotype-phenotype correlation of hereditary multiple exostoses." Clin Genet 70(2): 122-30. PubMed ID: 16879194
- Porter, D. E., et.al. (2004). "Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study." J Bone Joint Surg Br 86(7): 1041-6. PubMed ID: 15446535
- Schmale, Gregory A (2008). "Hereditary Multiple Osteochondromas."
- Vink, G. R., et.al. (2005). "Mutation screening of EXT1 and EXT2 by direct sequence analysis and MLPA in patients with multiple osteochondromas: splice site mutations and exonic deletions account for more than half of the mutations." Eur J Hum Genet 13(4): 470-4. PubMed ID: 15586175
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
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ORDER OPTIONS
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