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Ehlers-Danlos Syndrome, Type IV via the COL3A1 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
COL3A1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3095COL3A181479 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Ehlers-Danlos syndrome type IV (EDS IV or Vascular EDS, OMIM# 130050) is characterized by thin, translucent skin; easy bruising; characteristic facial appearance; and arterial, intestinal, or uterine fragility (Pepin & Byers. GeneReviews. 2011). Vascular dissection or rupture, gastrointestinal perforation, or organ rupture are the presenting signs in the majority of adults identified to have EDS IV. In childhood, inguinal hernia, pneumothorax, and recurrent joint subluxation or dislocation can occur. Pregnancy for women with EDS type IV has as much as a 12% risk for death from peripartum arterial rupture or uterine rupture.

Genetics

EDS IV is inherited in an autosomal dominant manner and is caused by variants in the COL3A1 gene. About half of affected individuals have inherited the variant from an affected parent, and the other half have a de novo COL3A1 variant. COL3A1 encodes the proα1(III) chain of type III procollagen, a major structural component of skin, blood vessels, and hollow organs. The type III procollagen molecule is a homotrimer; COL3A1 variants typically result in a structural alteration of type III collagen that leads to intracellular storage and impaired secretion of collagen chains. The majority of identified variants result in substitution of other amino acids for glycine residues in the Gly-X-Y triplets of the triple helical domain.

In one recent study, 410 unique COL3A1 variants were identified in 572 out of 630 clinical diagnosed EDS vascular type families. Among the families with COL3A1 variants, ~62% (356/572) carried a variant affecting glycine in the Gly-X-Y triple helix domain; ~29% (164/542) had splicing site variant (donor site: 144/164, acceptor site 20/164); ~ 7% (42/572) had small deletion/insertions; and 10 families had large deletions detected by MLPA method (Pepin et al. 2014).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to detect disease variants in at least 95% of individuals with EDS IV (Pepin & Byers. GeneReviews. 2011).

About 2% of individuals with EDS IV have large deletions involving single or multiple exons. So far, less than 10 large deletions have been reported in COL3A1 (Meienberg et al. 2010; Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the COL3A1 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 or biochemical features consistent with EDS IV, and family members of patients who have known COL3A1 variants.

Gene

Official Gene Symbol OMIM ID
COL3A1 120180
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ehlers-Danlos Syndrome, Type 4 AD 130050

Related Tests

Name
Comprehensive Cardiology Panel
Familial Thoracic Aortic Aneurysm and Dissection (TAAD) Panel

Citations

  • Human Gene Mutation Database (Bio-base).
  • Meienberg J, Rohrbach M, Neuenschwander S, Spanaus K, Giunta C, Alonso S, Arnold E, Henggeler C, Regenass S, Patrignani A, Azzarello-Burri S, Steiner B, et al. 2010. Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency. Eur J Hum Genet 18: 1315-1321. PubMed ID: 20648054
  • Pepin MG, Byers PH. 2011. Ehlers-Danlos Syndrome Type IV. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301667
  • Pepin MG, Schwarze U, Rice KM, Liu M, Leistritz D, Byers PH. 2014. Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Genet. Med. PubMed ID: 24922459

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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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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