• Test Code:
    1700
  • Department:
  • Test Synonyms:
    BMPR1A full gene sequencingJuvenile polyposis syndrome sequencing
  • CPT Code(s):
    81479
Background:

Juvenile polyposis syndrome is a rare (approximately 1 in 100,000 individuals), autosomal-dominant syndrome characterized by gastrointestinal polyps as well as an increased risk of colorectal cancer. Juvenile polyps are distinct in their hamartomatous nature and histology, in addition, juvenile polyps are commonly located in the colon and rectum. Mutations of BMPR1A as well as SMAD4 have been found in individuals affected with JPS. Most mutations of these mutations are small mutations (point mutations and small indels), with a smaller rate of larger aberrations impacting multiple exons or the entire gene. Small mutations of BMPR1A are identified in approximately 20% of JPS cases while larger aberrations are identified in approximately 2-11% of patients.

Reasons for Referral:

  • Identification of inherited genetic defects in BMPR1A in patients with multiple juvenile polyps
  • Confirmation of a suspected diagnosis with a positive family history of juvenile polyps when a familial mutation is known
  • Predispositional testing for asymptomatic family members with a positive family history of juvenile polyps

Methodology:

Next generation sequencing will analyze the exons or coding regions of the BMPR1A gene using Illumina NextSeq 500 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.

OR 

Sequencing for BMPR1A is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing.  The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions.  All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity.   

JPS genes (BMPR1A and SMAD4) may be sequenced individually or as a panel.

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):

  • Adult: 5mL
  • Child: 5mL
  • Infant: 2-3mL

DNA: 10µg at a minimum of 100ng/µL
Saliva: 1 ORAgene Saliva Kit (OGR-500)
Skin Fibroblasts: Punch Biopsy, or 2 T-25 confluent flasks

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

14 - 21 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. Aretz S, et al. High proportion of large genomic deletions and a genotype-phenotype update in 80 unrelated families with juvenile polyposis syndrome.J Med Genet 2007; 44: 702-709.
  2. Calva-Cerqueira D, et al. The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis. Clin Genet 2009: 79-85.
  3. Howe, J et al. The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. J Med Genet 2004; 41: 484-491.
  4. van Hattem W, et al. Large genomic deletions of SMAD4, BMPR1A, and PTEN in juvenile polyposis. Gut 2008; 57: 623-627.

 

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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