Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication
Ordering Recommendation
Diagnostic testing for juvenile polyposis syndrome/ hereditary hemorrhagic telangiectasia.  Predictive testing for juvenile polyposis syndrome/ hereditary hemorrhagic telangiectasia.
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Within 35 days  
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B).  
Specimen Preparation
Transport 3 mL whole blood. (Min: 2 mL)  
Storage/Transport Temperature
Unacceptable Conditions
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
Interpretive Data
Background Information for Juvenile Polyposis (SMAD4) Sequencing and 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.
1 in 16,000 to 1 in 100,000 for JPS; unknown for JP/HHT.
Autosomal dominant; de novo mutations occur in 25 percent of JPS.
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 25 percent for JPS; unknown for JP/HHT.
: Bidirectional sequencing of the entire SMAD4 coding region and intron-exon boundaries. Multiplex ligation-dependent probe amplification (MLPA) to detect large SMAD4 coding region deletions/duplications.
Analytical Sensitivity and Specificity
: 99 percent.
Diagnostic errors can occur due to rare sequence variations. Breakpoints for large deletions/duplications will not be determined.

See Compliance Statement C:
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.
CPT Code(s)
81405; 81406
Component Test Code*Component Chart NameLOINC
2001973JPS (SMAD4) Seq and Del/Dup Interp 
2001975SMAD4 FGA 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 sqeuending and deletion/duplication