Juvenile Polyposis (SMAD4) Deletion/Duplication (INACTIVE as of 05/15/17: Refer to 2001971)
Ordering Recommendation

This is a second tier test and REQUIRES PERMISSION from  ARUP's Genetic Counselor (800-242-2787, x2141) before ordering. Preferred initial test is the sequencing and deletion/duplication test.

Polymerase Chain Reaction/Multiplex Ligation-dependent Probe Amplification
Within 14 days
New York DOH Approval Status
This test is New York DOH approved.
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
Lavender (EDTA), 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: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable 
Reference Interval
By report
Interpretive Data
Background Information for Juvenile Polyposis (SMAD4) Deletion/Duplication:
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 10 percent for JPS; unknown for JP/HHT.
Methodology: Multiplex ligation-dependent probe amplification (MLPA) to detect large SMAD4 coding region deletions/duplications.
Analytical Sensitivity and Specificity: 90 and 99 percent, respectively.
Limitations:Diagnostic errors can occur due to rare sequence variations. Breakpoints for large deletions/duplications will not be determined. SMAD4 base pair substitutions, small deletions/duplications, deep intronic, and regulatory region mutations will not be detected.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Component Test Code*Component Chart NameLOINC
2001978JPS (SMAD4) Deletion/Dupliction Interp
2001979SMAD4 DD Specimen
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
  • SMAD4
  • SMAD4 deletion/duplication assay