Juvenile Polyposis Syndrome (BMPR1A) Sequencing and Deletion/Duplication

Background Information for: Juvenile Polyposis Syndrome (BMPR1A) Sequencing and Deletion/Duplication:
Characteristics: Multiple juvenile (hamartomatous) polyps in the stomach, small intestine, colon, and rectum. Risk for colon cancer is 20 percent by age 35 and 70 percent by age 60.
Incidence: 1 in 16,000 to 100,000 individuals.
Inheritance: Autosomal dominant.
Penetrance: Greater than 90 percent for polyp development.
Cause: Pathogenic BMPR1A and SMAD4 mutations.
Clinical Sensitivity: 20-25 percent. 
Methodology: Bidirectional sequencing of the entire BMPR1A coding region and intron-exon boundaries. Multiplex ligation-dependent probe amplification (MLPA) to detect large BMPR1A coding region deletions and duplications.
Analytical Sensitivity & Specificity for Sequencing and MLPA: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. Large deletions/duplications of exons 7 and 8 may not be detected. The breakpoints of large deletions/duplications will not be determined. Mutations in genes other than BMPR1A are not evaluated. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.