Juvenile Polyposis Syndrome (JPS) via BMPR1A 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 | |
|---|---|---|---|---|---|
| 7391 | BMPR1A | 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
Juvenile polyposis syndrome (JPS; OMIM 608456) is a rare, inherited hamartomatous polyposis syndrome with increased susceptibility to colorectal cancer. Clinical diagnosis of JPS is typically made when one of the following criteria is met: more than five juvenile polyps in the colorectum; multiple juvenile polyps throughout the GI tract; or any number of juvenile polyps and a family history of gastrointestinal polyps (Chow & Macrae J Gastroenterol Hepatol 20:1634-1640, 2005). Juvenile refers to the developmentally immature nature of the polyp, not the age of disease onset. In addition to polyposis, 10-20% of JPS patients also have extracolonic abnormalities such as congenital heart defects, cleft lip or palate, microcephaly, and malrotations (Eng et al. Annu Rev Med 52:371-400, 2001). Although a solitary juvenile polyp in the general population has very little malignant potential (Nugent et al. Gastroenterol 105:698-700, 1993), patients with JPS have a 68% chance of developing gastrointestinal cancer by the age of 60 (Chow & Macrae J Gastroenterol Hepatol 20:1634-1640, 2005). Thus, confirming a diagnosis of JPS is important for appropriate surveillance and management of cancer in individuals with juvenile polyps.
Genetics
Juvenile polyposis syndrome is caused by heterozygous germline variants in either BMPR1A (OMIM 601299) or SMAD4 (OMIM 600993; Howe et al. Science 280:1086-1088, 1998; Howe et al. Nat Genet 28:184-187, 2001). Both genes mediate the biological effects of the transforming growth factor-β (TGF-β) superfamily of cytokines (Miyazono et al. J Biochem 147:35-51, 2010). In epithelial cells, the TGF-β pathway normally inhibits growth and proliferation; variants in BMPR1A or SMAD4 decrease TGF-β signaling and lead to neoplasia and carcinoma. BMPR1A encodes a transmembrane serine/threonine kinase receptor that binds the bone morphogenetic protein (BMP) subfamily of TGF-β ligands (Heldin et al. Nature 390:465-471, 1997). Approximately 70 pathogenic variations have been identified throughout the BMPR1A gene and most (~90%) are detectable by DNA sequencing (Human Gene Mutation Database; www.hgmd.cf.ac.uk). In addition to causing JPS, one BMPR1A variant (p.Ala338Asp) has also been identified in a family with Cowden syndrome (CS; OMIM 158350), indicating BMPR1A variants might also define a small subset of CS cases (Zhou et al. Am J Hum Genet 69:704-711, 2001).
Clinical Sensitivity - Sequencing with CNV PG-Select
This test is predicted to identify a BMPR1A variant in ~20% of patients diagnosed with JPS (Calva-Cerqueira et al., Clin Genet 75:79-85, 2009). Gross deletions/duplications can represent between 2-11% (Haidle and Howe. GeneReviews. 2011) of BMPR1A variants.
Testing Strategy
This test provides full coverage of all coding exons of the BMPR1A 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 diagnosed with JPS and relatives of patients with a known BMPR1A variant. Cowden syndrome patients who have tested negative for a PTEN variant are also candidates. This test is specifically designed to detect germline variants and is not appropriate for the detection of somatic variants in polyp/tumor tissue.
Candidates for this test are patients diagnosed with JPS and relatives of patients with a known BMPR1A variant. Cowden syndrome patients who have tested negative for a PTEN variant are also candidates. This test is specifically designed to detect germline variants and is not appropriate for the detection of somatic variants in polyp/tumor tissue.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| BMPR1A | 601299 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Hereditary Mixed Polyposis Syndrome 2 | AD | 610069 |
| Juvenile Polyposis Syndrome | AD | 174900 |
Citations
- Calva-Cerqueira D, Chinnathambi S, Pechman B, Bair J, Larsen-Haidle J, Howe J. 2009. The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis. Clinical Genetics 75: 79–85. PubMed ID: 18823382
- Chow E, Macrae F. 2005. A review of Juvenile Polyposis Syndrome. Journal of Gastroenterology and Hepatology 20: 1634–1640. PubMed ID: 16246179
- Eng C, Hampel H, Chapelle A de la. 2001. Genetic testing for cancer predisposition. Annual review of medicine 52: 371–400. PubMed ID: 11160785
- Heldin C-H, Miyazono K, Ten Dijke P. 1997. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 390: 465–471. PubMed ID: 9393997
- Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE, Traverso G, Vogelstein B. 2001. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat. Genet. 28: 184–187. PubMed ID: 11381269
- Howe JR. 1998. Mutations in the SMAD4/DPC4 Gene in Juvenile Polyposis. Science 280: 1086–1088. PubMed ID: 9582123
- Human Gene Mutation Database.
- Larsen Haidle J, Howe JR. 2011. Juvenile Polyposis Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301642
- Miyazono K, Kamiya Y, Morikawa M. 2009. Bone morphogenetic protein receptors and signal transduction. Journal of Biochemistry 147: 35–51. PubMed ID: 19762341
- Nugent, K. P., et.al. 1993. Solitary juvenile polyps: not a marker for subsequent malignancy. Gastroenterology 105(3): 698-700. PubMed ID: 8395444
- Zhou et.al. 2001. Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. Am J Hum Genet 69(4): 704-11. PubMed ID: 11536076
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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