#ExistInterpData>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.
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 25 percent for JPS; unknown for JP/HHT.
Methodology: 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.
Limitations: Rare diagnostic errors can occur due to primer or probe site mutations. Breakpoints for large deletions/duplications will not be determined.
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
||SMAD4 (Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication)