Mutations in the SMAD4 gene have been found in patients with Juvenile Polyposis Syndrome (JPS) (~20 percent), patients with combined Juvenile Polyposis/ Hereditary Hemorrhagic Telangiectasia (JP/HHT) (100 percent, based on small numbers) or patients with HHT, but without reported symptoms of JPS (2-3 percent, based on small numbers).
JPS is an autosomal dominant condition characterized by the presence of more than five hamartomatuous polyps in the rectum, colon, or GI tract. Affected individuals may experience abdominal pain, diarrhea, rectal bleeding, anemia, and have an increased risk of developing gastrointestinal cancers. HHT is characterized by recurrent nosebleeds, telangiectases (mouth, face, hands, GI tract), and arteriovenous malformations (lung, brain, liver, spine). Arteriovenous malformations (AVMs) are usually congenital, while nosebleeds and external telangiectases often do not present until the second or third decade of life. JP/HHT is characterized by symptoms of both diseases in one or more family members of the same family.
The purpose of this database is to document all known SMAD4 mutations or gene variants including sequence based changes and large deletion/duplications that have been linked to JPS, JP/HHT or HHT, as well as any available associated clinical information or significant literature related to the disorder. The Genbank sequences NC_000018.9, NM_005359.5, and NP_005350.1 were used as reference sequences.
A collaboration between ARUP Laboratories and Ambry Genetics, analyzing a total of 4672 clinical cases for SMAD4 copy number analysis, found evidence of a SMAD4 processed pseudogene in 0.26% of the cases.
ARUP Laboratories offers the following testing:
- Deletion Duplication (test 2001976)
- Sequencing (test 0051510)
- Sequencing and Deletion/Duplication (test 2001971)
The SMAD4 database currently has 88 total entries.
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