Multiple Epiphyseal Dysplasia Panel
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Panel CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
10247 | Genes x (10) | 81479 | 81479(x20) | $990 | Order Options and Pricing |
Pricing Comments
We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.
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).
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
Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous chondrodysplasia with either autosomal dominant or recessive inheritance. Dominant MED (ADMED) occurs early in childhood and usually involves pain in the hips and/or knees after exercise. Some patients may have a waddling gait. Adult height can be in the lower range of normal or mildly shortened. The limbs are relatively short in comparison to the trunk. Other features may include progressive pain and joint deformity which can lead to early-onset osteoarthritis. ADMED is caused by pathogenic variants in the COMP, MATN3, COL9A1, COL9A2, COL9A3 and COL2A1 genes (Briggs et al. 2019. PubMed ID: 20301302).
Recessive MED (ARMED) is characterized by joint pain (usually in the hips or knees) occurring in late childhood. Malformations of hands, feet, and knees; and scoliosis may also be observed. Height is usually within the normal range prior to puberty; Adult height can range from 150 to 180 cm. Pathogenic variants in the SCL26A2 gene have been reported in patients with ARMED (Hauer et al. 2018. PubMed ID: 29758562; Bonafé et al. 2014. PubMed ID: 20301483). Pathogenic variants in the CANT1, DDR2 and UFSP2 gene have been reported in ARMED and autosomal recessive spondylo-meta-epiphyseal dysplasia (Balasubramanian et al. 2017. PubMed ID: 28742282; Bargal et al. 2009. PubMed ID: 19110212; Di Rocco et al 2018. PubMed ID: 28892125; Watson et al. 2015. PubMed ID: 26428751).
Genetics
Pathogenic variants in COMP, MATN3 and type IX collagen genes (COL9A1, COL9A2 and COL9A3) account for 70% , ~20% and ~10% of ADMED, respectively (Jackson et al. 2012. PubMed ID: 21922596; Briggs et al. 2019. PubMed ID: 20301302). Pathogenic variants in SLC26A2 mainly cause autosomal recessive diastrophic dysplasia and a few have been reported in patients with ARMED and other conditions (Rossi and Superti-Furga. 2001. PubMed ID: 11241838; Bonafe et al. 2015. PubMed ID:26394607). In addition to MED, pathogenic variants in these genes also cause other skeletal dysplasia disorders. These skeletal disorders have overlapping clinical features with MED, which causes difficulties in reaching a correct clinical diagnosis. Molecular diagnosis of the skeletal dysplasia subtypes is also complex because extensive genetic heterogeneity exists for each disorder (Bonafe et al. 2015. PubMed ID:26394607). Considering the clinical and genetic heterogeneity, a molecular testing approach that interrogates all known MED genes is highly recommended.
Pathogenic variants in CANT1 have been mainly reported in patients with autosomal recessive desbuquois dysplasia (Huber et al. 2009. PubMed ID: 19853239). To date, only two homozygous missense variants were reported in two families with MED (Balasubramanian et al. 2017. PubMed ID: 28742282).
Pathogenic variants in DDR2 have been reported in patients with autosomal recessive spondylo-meta-epiphyseal dysplasia (Bargal et al. 2009. PubMed ID: 19110212).
A few missense variants in UFSP2 have been reported in patients with autosomal dominant Spondyloepimetaphyseal dysplasia (Di Rocco et al 2018. PubMed ID: 28892125; Watson et al. 2015. PubMed ID: 26428751).
See individual gene test descriptions for information on molecular biology of gene products.
Clinical Sensitivity - Sequencing with CNV PGxome
Causative variants in COMP, MATN3 and type IX collagen genes (COL9A1, COL9A2 and COL9A3) account for 70% , ~20% and ~10% of dominant Multiple Epiphyseal Dysplasia (MED), respectively (Jackson et al. 2012. PubMed ID: 21922596; Briggs et al. 2019. PubMed ID: 20301302). To date, only two missense variants in COL2A1 have been reported in MED patients (Jackson et al. 2012. PubMed ID: 21922596).
The sensitivity for large deletions and duplications may be low, because only a few cases with large deletions and insertions involving the COL9A3, COMP and COL2A1 genes have been reported (Van der Hout et al. 2002. PubMed ID: 12204008; Human Mutation Database).
Testing Strategy
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This panel provides 100% coverage of all coding exons of the genes 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 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 clinical and radiologic features consistent with MED and related disorders. This test especially aids in a differential diagnosis of similar phenotypes, rules out particular syndromes, and provides the analysis of multiple genes simultaneously. Individuals who are suspected of any of these disorders, especially if clinical diagnosis is unclear, and individuals who have been found to be negative by mutation analysis for single gene tests are also candidates.
Candidates for this test are patients with clinical and radiologic features consistent with MED and related disorders. This test especially aids in a differential diagnosis of similar phenotypes, rules out particular syndromes, and provides the analysis of multiple genes simultaneously. Individuals who are suspected of any of these disorders, especially if clinical diagnosis is unclear, and individuals who have been found to be negative by mutation analysis for single gene tests are also candidates.
Genes
Official Gene Symbol | OMIM ID |
---|---|
CANT1 | 613165 |
COL2A1 | 120140 |
COL9A1 | 120210 |
COL9A2 | 120260 |
COL9A3 | 120270 |
COMP | 600310 |
DDR2 | 191311 |
MATN3 | 602109 |
SLC26A2 | 606718 |
UFSP2 | 611482 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Related Test
Name |
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PGxome® |
Citations
- Balasubramanian et al. 2017. PubMed ID: 28742282
- Bargal et al. 2009. PubMed ID: 19110212
- Bargal et al. 2009. PubMed ID: 19110212
- Bonafé et al. 2014. PubMed ID: 20301483
- Bonafe et al. 2015. PubMed ID: 26394607
- Briggs et al. 2019. PubMed ID: 20301302
- Di Rocco et al 2018. PubMed ID: 28892125
- Hauer et al. 2018. PubMed ID: 29758562
- Huber et al. 2009. PubMed ID: 19853239
- Human Gene Mutation Database (Bio-base).
- Jackson et al. 2012. PubMed ID: 21922596
- Rossi and Superti-Furga. 2001. PubMed ID: 11241838
- Van Der Hout et al. 2002. PubMed ID: 12204008
- Watson et al. 2015. PubMed ID: 26428751
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
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.