Juvenile Polyposis (SMAD4) Deletion/Duplication
2001976
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.
Mnemonic
SMAD4 DD
Methodology
Polymerase Chain Reaction/Multiplex Ligation-dependent Probe Amplification
Performed
Varies
Reported
Within 14 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
 
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B).  
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL)  
Storage/Transport Temperature
Refrigerated.  
Unacceptable Conditions
 
Remarks
 
Stability
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.



Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

See Compliance Statement C: www.aruplab.com/CS
Note
CPT Code(s)
81405
Components
Component Test Code*Component Chart Name
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.
Cross References
  • SMAD4
  • SMAD4 deletion/duplication assay