title: Germline mutations of the dpc4 gene in Korean juvenile polyposis patients.
abstract: Juvenile polyposis is an uncommon condition characterized by the development of multiple (usually more than 5) juvenile polyps in the gastrointestinal tract, especially in the colon. This disease usually occurs during childhood, and is inherited in an autosomal dominant fashion. It has been suggested that the dpc4 (deleted in pancreatic carcinoma, locus 4) gene, which is located on chromosome 18q21.1, might cause juvenile polyposis. The dpc4 (smad4) gene is a candidate tumor-suppressor gene and may play a role in the TGF-beta-signaling pathway. To confirm the idea that alterations of the dpc4 gene may result in juvenile polyposis, we screened 5 Korean juvenile-polyposis patients by PCR-SSCP (single-strand conformation polymorphism) analysis and bi-directional sequencing. There were germline mutations of the dpc4 gene in 3 out of the 5 patients: 2 had a genetic alteration in exon 9 and the third had a mutation in exon 8. These germline mutations occurred in the C-terminus of the dpc4 gene, similar to most published mutations. One patient exhibited a non-sense mutation (codon 388), which changed a glutamine codon (CAG) to a stop codon (TAG). The second patient harbored a mis-sense mutation (codon 390), causing a non-conservative amino-acid change <glutamate (GAA) to lysine (AAA)>. The third patient had a mis-sense mutation in exon 8 (codon 361), which altered an arginine codon (CGC) into a histidine codon (CAC).
authors.affiliation: Korean Hereditary Tumor Registry, Laboratory of Cell Biology, Cancer Research Center and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: I J
authors.initials: IJ
authors.lastname: Kim
authors.forename: J L
authors.initials: JL
authors.lastname: Ku
authors.forename: K A
authors.initials: KA
authors.lastname: Yoon
authors.forename: S C
authors.initials: SC
authors.lastname: Heo
authors.forename: S Y
authors.initials: SY
authors.lastname: Jeong
authors.forename: H S
authors.initials: HS
authors.lastname: Choi
authors.forename: K H
authors.initials: KH
authors.lastname: Hong
authors.forename: S K
authors.initials: SK
authors.lastname: Yang
authors.forename: J G
authors.initials: JG
authors.lastname: Park
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators