Diagnostic and predictive testing for juvenile polyposis syndrome (JPS) or JPS/hereditary hemorrhagic telangiectasia.
- Patient Preparation
- Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Characteristics of Juvenile Polyposis Syndrome (JPS): Gastrointestinal (GI) bleeding, multiple hamartomatous polyps in the GI tract, increased risk for GI carcinoma.
Characteristics of JP/Hereditary Hemorrhagic Telangiectasia (HHT): Recurrent nosebleeds, telangiectases (mouth, face, hands, GI tract), arteriovenous malformations (lung, brain, liver, spine) and hamartomatous polyps in the GI tract.
Incidence: 1 in 16,000 to 1 in 100,000 for JPS; unknown for JP/HHT.
Inheritance: Autosomal dominant; de novo mutations occur in 25 percent of JPS.
Penetrance: Suspected to be greater than 90 percent for JPS.
Cause for JPS: Mutations in SMAD4, BMPR1A, and other unknown genes.
Cause for JP/HHT: Mutations in SMAD4.
Clinical Sensitivity: Approximately 20 percent for JPS; unknown for JP/HHT.
Methodology: Bidirectional sequencing of the entire coding region and intron/exon boundaries of the SMAD4 gene.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletion/duplications will not be detected. Mutations in genes other than SMAD4 will not be detected. 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.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|0051509||Juvenile Polyposis (SMAD4) Sequencing|
|2001377||SMAD4 SEQ Specimen|
- SMAD4 sequencing