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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7391 BMPR1A 81479 81479,81479 $540 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7391BMPR1A81479 81479(x2) $540 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days 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

  • Hannah Cox, PhD

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.

Gene

Official Gene Symbol OMIM ID
BMPR1A 601299
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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