Distal Arthrogryposis Type 5D (DA5D) via the ECEL1 Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
11279 | ECEL1 | 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
Distal arthrogryposis (DA) syndromes are a group of multiple congenital contracture disorders with distal joint involvement and variable clinical expression. Distal arthrogryposis type 5D (DA5D) is an autosomal recessive DA syndrome with unique facial features (McMillin et al. 2013. PubMed ID: 23261301). Clinical features include congenital contractures affecting mostly distal joints of upper and lower limbs, club feet, hip dislocation, short stature, and scoliosis. Campdodacytly is more severe in the fingers than the toes with the wrist and thumbs being adducted. Additional findings include ptosis, severe ophthalmoplegia, astigmatism, micrognathia, tongue groove, and cleft palate (Ullmann et al. 2018. PubMed ID: 30131190). A more severe presentation of multiple pterygia and fetal arthrogryposis has also been reported (Bayram et al. 2016. PubMed ID: 26752647).
Genetics
Distal arthrogryposis type 5D is inherited in an autosomal recessive manner. Reported causative variants include missense, nonsense, splicing, and small frameshift deletions/duplications and indels that result in premature protein termination (Human Gene Mutation Database).
The ECEL1 gene encodes the endothelin-converting enzyme-like 1 (ECEL1), a type II integral transmembrane zinc metalloprotease. The ECEL1 protein localizes to the brain and peripheral nerves during fetal development and is thought to play a role in neural and neuromuscular junction development (Dieterich et al. 2013. PubMed ID: 23236030; McMillin et al. 2013. PubMed ID: 23261301).
Clinical Sensitivity - Sequencing with CNV PGxome
Five of seven families with the features of distal arthrogryposis type 5D were found to have ECEL1 pathogenic variants (McMillin et al. 2013. PubMed ID: 23261301). In another study, six families were found to have ECEL1 pathogenic variants among a cohort of 20 families with non-specific distal arthrogryposis (Dieterich et al. 2013. PubMed ID: 23236030). In a larger cohort of 38 families with fetal akinesia, arthrogryposis, or severe congenital myopathy, one family was found to harbor ECEL1 pathogenic variants (Todd. 2015. PubMed ID: 26578207). To date, no gross deletions or duplications in the ECEL1 gene have been reported (Human Gene Mutation Database). All coding and non-coding regions of the ECEL1 gene that harbor causative variants reported in the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk/) as of 06/28/2019 are covered by this test.
Testing Strategy
This test provides full coverage of all coding exons of the ECEL1 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
Individuals with clinical symptoms consistent with distal arthrogryposis and facial features consistent with DA5D. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ECEL1.
Individuals with clinical symptoms consistent with distal arthrogryposis and facial features consistent with DA5D. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ECEL1.
Gene
Official Gene Symbol | OMIM ID |
---|---|
ECEL1 | 605896 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Arthrogryposis, distal, type 5D | AR | 615065 |
Citations
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.