PT - JOURNAL ARTICLE AU - S Bevan AU - K Woodford-Richens AU - P Rozen AU - C Eng AU - J Young AU - M Dunlop AU - K Neale AU - R Phillips AU - D Markie AU - M Rodriguez-Bigas AU - B Leggett AU - E Sheridan AU - S Hodgson AU - T Iwama AU - D Eccles AU - W Bodmer AU - R Houlston AU - I Tomlinson TI - Screening <em>SMAD1</em>,<em>SMAD2</em>, <em>SMAD3</em>, and<em>SMAD5</em> for germline mutations in juvenile polyposis syndrome AID - 10.1136/gut.45.3.406 DP - 1999 Sep 01 TA - Gut PG - 406--408 VI - 45 IP - 3 4099 - http://gut.bmj.com/content/45/3/406.short 4100 - http://gut.bmj.com/content/45/3/406.full SO - Gut1999 Sep 01; 45 AB - BACKGROUND AND AIMS Juvenile polyps occur in several Mendelian disorders, whether in association with gastrointestinal cancer alone (juvenile polyposis syndrome, JPS) or as part of known syndromes (Cowden, Gorlin, and Bannayan-Zonana) in association with developmental abnormalities, dysmorphic features, or extraintestinal tumours. Recently, some JPS families were shown to harbour germline mutations in theSMAD4 (DPC4) gene, providing further evidence for the importance of the TGFβ signalling pathway in colorectal cancer. There remains, however, considerable, unexplained genetic heterogeneity in JPS. Other members of the SMAD family are excellent candidates for JPS, especiallySMAD2 (which, likeSMAD4, is mutated somatically in colorectal cancers), SMAD3 (which causes colorectal cancer when “knocked out” in mice),SMAD5, and SMAD1.METHODS SMAD1,SMAD2, SMAD3, andSMAD5 were screened for germline mutations in 30 patients with JPS and without SMAD4mutations.RESULTS No mutations were found in any of these genes. A G–A C89Y polymorphism with possible effects on protein function was found in SMAD3, but the frequencies of the G and A alleles did not differ between patients with JPS and controls.CONCLUSIONS It remains to be determined whether or not this polymorphism is involved in a minor predisposition to colorectal or other carcinomas.SMAD4 may be the only member of the SMAD family which causes JPS when mutant in the germline. The other genes underlying JPS remain to be identified.CSGEconformation specific gel electrophoresisJPSjuvenile polyposis syndromeTGFtransforming growth factor