Loeys-Dietz Syndrome via the SMAD3 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7319 | SMAD3 | 81479 | 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.
Clinical Features and Genetics
Clinical Features
Loeys-Dietz syndrome (LDS) is characterized by two major clinical features: vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections) and skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus). Additional variable features include craniofacial abnormalities (ocular hypertelorism, bifid uvula/cleft palate and craniosynostosis) and cutaneous findings (translucent skin, easy bruising and dystrophic scars) (Loeys et al. 2005. PubMed ID: 15731757). Two clinical entities of LDS have been described (types 1 and 2), which represent a continuum of clinical features. Approximately 75% of patients with LDS type 1 have craniofacial manifestations, while approximately 25% of patients with LDS type 2 have cutaneous manifestations (Loeys et al. 2005. PubMed ID: 15731757; Loeys et al. 2006. PubMed ID: 16928994). LDS is usually characterized by aggressive arterial aneurysms (mean age at death is 26.1 years) and high incidence of pregnancy-related complications including death and uterine rupture (Loeys et al. 2005. PubMed ID: 15731757). Clinical features of LDS overlap with Marfan syndrome (Loeys et al. 2005. PubMed ID: 15731757; Loeys and Dietz. 2013. PubMed ID: 20301312).
Genetics
LDS is inherited in an autosomal dominant manner due to pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3 (Loeys et al. 2005. PubMed ID: 15731757; Mizuguchi et al. 2004. PubMed ID: 15235604; Rienhoff et al. 2013. PubMed ID: 23824657). TGFBR1, TGFBR2, SMAD3, and TGFB2 are all involved in TGFβ signaling. TGFB2 is a cytokine, TGFBR1 and TGFBR2 are receptors and SMAD3 is a signal transducer and transcription factor. The majority of documented causative variants in TGFBR1, TGFBR2, and SMAD3 are missense (Loeys et al. 2005. PubMed ID: 15731757; Loeys et al. 2006. PubMed ID: 16928994; Stheneur et al. 2008. PubMed ID: 18781618; Lerner-Ellis et al. 2014. PubMed ID: 24793577). SMAD3 is also associated with aneurysms-osteoarthritis syndrome, a syndromic form of thoracic aortic aneurysm and dissection with arterial tortuosity, skeletal and craniofacial defects, cutaneous abnormalities and early-onset osteoarthritis (van de Laar et al. 2011. PubMed ID: 21217753; van de Laar et al. 2012. PubMed ID: 22167769). Approximately 25% of LDS cases are familial and 75% of cases are de novo (Loeys and Dietz. 2013. PubMed ID: 20301312).
Clinical Sensitivity - Sequencing with CNV PG-Select
Approximately 95% of Loeys-Dietz cases are found to have a pathogenic variant in TGFBR1, TGFBR2, SMAD3, TGFB2, or TGFB3 (Loeys and Dietz. 2013. PubMed ID: 20301312). Approximately 5-10% of cases have a pathogenic variant in SMAD3 (Loeys and Dietz. 2013. PubMed ID: 20301312).
Testing Strategy
This test provides full coverage of all coding exons of the SMAD3 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 symptoms consistent with Loeys-Dietz syndrome and family members of patients with these symptoms.
Candidates for this test are patients with symptoms consistent with Loeys-Dietz syndrome and family members of patients with these symptoms.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SMAD3 | 603109 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Loeys-Dietz Syndrome 3 | AD | 613795 |
Related Tests
| Name |
|---|
| Comprehensive Cardiology Panel |
| Familial Thoracic Aortic Aneurysm and Dissection (TAAD) Panel |
| Loeys-Dietz Syndrome Panel |
| Sudden Cardiac Arrest Panel |
Citations
- Lerner-Ellis et al. 2014. PubMed ID: 24793577
- Loeys and Dietz. 2013. PubMed ID: 20301312
- Loeys et al. 2005. PubMed ID: 15731757
- Loeys et al. 2006. PubMed ID: 16928994
- Mizuguchi et al. 2004. PubMed ID: 15235604
- Rienhoff et al. 2013. PubMed ID: 23824657
- Stheneur et al. 2008. PubMed ID: 18781618
- van de Laar et al. 2011. PubMed ID: 21217753
- van de Laar et al. 2011.
- van de Laar et al. 2012. PubMed ID: 22167769
- van de Laar et al. 2012.
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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