Metaphyseal Chondrodysplasia, Schmid Type (MCDS) via the COL10A1 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 | |
|---|---|---|---|---|---|
| 8771 | COL10A1 | 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
Schmid-type metaphyseal chondrodysplasia (OMIM#156500) is characterized by short stature with relatively short limbs, bowed legs, and a waddling gait. Radiographic findings include shortening of the tubular bones, anterior cupping, sclerosis and splaying of the ribs, and diffuse metaphyseal flaring and irregularity that is most pronounced at the knees, coxa vara, and femoral bowing (Elliott et al. Am J Med Genet 132A: 191-193, 2005).
Genetics
MCDS is inherited in an autosomal dominant manner and is caused by variants in the COL10A1 gene. COL10A1 encodes collagen X α1-chain, which is comprised of a collagenous domain (COL1) flanked by a short N-terminal noncollagenous domain (NC2) and a C-terminal noncollagenous domain (NC1). Three identical α1(X)-chains form the homotrimer collagen X, which assembly is facilitated by the interaction of the NC1 domain. COL10A1 variants have been shown to cluster in the 3’ region of exon 3 (NC1 domain). They are about equally divided into two types, missense variants and variants that introduce premature termination signals (Bateman et al. Hum Mutat 25:525-534, 2005). Both haploinsufficiency and dominant-negative effects have been documented to be the molecular basis of MCDS (Chan et al. J Biol Chem 276: 7992-7997, 2001; Gregory et al. J Med Genet 37: 627-629, 2000). Variants in COL10A1 can also cause spondylometaphyseal dysplasia, Japanese type (Ikegawa et al. Am J Med Genet 63: 1659-1662, 1998), which has overlapping skeletal features with MCDS.
Clinical Sensitivity - Sequencing with CNV PGxome
This test is predicted to detect disease variants in more than half of individuals with a clinical diagnosis of MCDS (Bonaventure et al. Hum Genet 96: 58-64, 1995; Wallis et al. J Med Genet 33: 450-457, 1996; Bateman et al. Hum Mutat 23: 396, 2004; Makitie et al. Am J Med Genet 137A:241-248, 2005).
Testing Strategy
This test provides full coverage of all coding exons of the COL10A1 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 clinical and radiographic features consistent with Schmid-type metaphyseal chondrodysplasia and family members of patients who have a known COL10A1 variant. Patients suspected to have cartilage-hair hypoplasia but without extra-skeletal findings and who tested negative for RMRP gene are also candidates for this test.
Candidates for this test are patients with clinical and radiographic features consistent with Schmid-type metaphyseal chondrodysplasia and family members of patients who have a known COL10A1 variant. Patients suspected to have cartilage-hair hypoplasia but without extra-skeletal findings and who tested negative for RMRP gene are also candidates for this test.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| COL10A1 | 120110 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Metaphyseal Chondrodysplasia, Schmid Type | AD | 156500 |
Citations
- Bateman, J. F., et.al. (2004). "Identification of four novel COL10A1 missense mutations in schmid metaphyseal chondrodysplasia: further evidence that collagen X NC1 mutations impair trimer assembly." Hum Mutat 23(4): 396. PubMed ID: 15024737
- Bateman, J. F., et.al. (2005). "Mutations of COL10A1 in Schmid metaphyseal chondrodysplasia." Hum Mutat 25(6): 525-34. PubMed ID: 15880705
- Bonaventure, J., et.al. (1995). "Mutations in three subdomains of the carboxy-terminal region of collagen type X account for most of the Schmid metaphyseal dysplasias." Hum Genet 96(1): 58-64. PubMed ID: 7607655
- Chan, D., et.al. (2001). "Aberrant signal peptide cleavage of collagen X in Schmid metaphyseal chondrodysplasia. Implications for the molecular basis of the disease." J Biol Chem 276(11): 7992-7. PubMed ID: 11115494
- Elliott, A. M., et.al. (2005). "Hand involvement in Schmid metaphyseal chondrodysplasia." Am J Med Genet A 132A(2): 191-3. PubMed ID: 15578582
- Gregory, C. A., et.al. (2000). "Equal expression of typ X collagen mRNA fom mutant and wild type COL10A1 alleles in growth plate cartilage from a patient with metaphyseal chondrodysplasia type Schmid." J Med Genet 37(8): 627-9. PubMed ID: 10991694
- Ikegawa, S., et.al. (1998). "Mutation of the type X collagen gene (COL10A1) causes spondylometaphyseal dysplasia." Am J Hum Genet 63(6): 1659-62. PubMed ID: 9837818
- Makitie, O., et.al. (2005). "Schmid type of metaphyseal chondrodysplasia and COL10A1 mutations--findings in 10 patients." Am J Med Genet A 137A(3): 241-8. PubMed ID: 16088909
- Wallis, G. A., et.al. (1996). "Mutations within the gene encoding the alpha 1 (X) chain of type X collagen (COL10A1) cause metaphyseal chondrodysplasia type Schmid but not several other forms of metaphyseal chondrodysplasia." J Med Genet 33(6): 450-7. PubMed ID: 8782043
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
Loading...
×
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.