RT Journal Article
SR Electronic
T1 Screening <em>SMAD1</em>,<em>SMAD2</em>, <em>SMAD3</em>, and<em>SMAD5</em> for germline mutations in juvenile polyposis syndrome
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 406
OP 408
DO 10.1136/gut.45.3.406
VO 45
IS 3
A1 S Bevan
A1 K Woodford-Richens
A1 P Rozen
A1 C Eng
A1 J Young
A1 M Dunlop
A1 K Neale
A1 R Phillips
A1 D Markie
A1 M Rodriguez-Bigas
A1 B Leggett
A1 E Sheridan
A1 S Hodgson
A1 T Iwama
A1 D Eccles
A1 W Bodmer
A1 R Houlston
A1 I Tomlinson
YR 1999
UL http://gut.bmj.com/content/45/3/406.abstract
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