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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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7091 EXT2 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7091EXT281479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

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

  • Stela Berisha, PhD, FACMG

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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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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