A Novel Germline Mutation in Exon 10 of the SMAD4 Gene in a Familial Juvenile Polyposis
A 21-year-old man presenting rectal bleeding visited our hospital. Based on initial laboratory results, his hemoglobin was mildly decreased of 12.7 g/dL, but no additional abnormalities were found. A colonoscopy indicated multiple colon polyps with hyperemic features (). Histological examination revealed hamartomatous polyps with cystically dilated glands, which were surrounded by stroma and showed prominent inflammatory cell infiltration (). Upper endoscopy identified the presence of other lesions and revealed numerous reddish polypoid lesions in the whole stomach (). To confirm small bowel involvement, capsule endoscopy was conducted and it showed numerous polypoid lesions in the jejunum and the ileum (). Endoscopic removal of gastric and colonic polyps was done. We planned the surveillance with upper endoscopy and colonoscopy every 1 to 2 years, and also planned the evaluation of small bowel every 2 to 3 years.\nThe patient's 47-year-old mother had a history of subtotal gastrectomy due to gastric polyposis with anemia 15 years earlier. She had also undergone a right hemicolectomy because of ascending colon cancer 2 years previously. A colonoscopy performed during that time indicated a pedunculated polyp, which is similar to the type of polyp found in her son (). The histological analysis of the polyps showed hamartomatous features that were consistent with juvenile polyposis () Upper endoscopy revealed multiple erythematous polyps in the stomach including cardia which are similar to her son ().\nGiven the clinicopathological findings and the family history, the diagnosis was FJP. Subsequently, written informed consent was obtained from both patients to perform genetic testing, and screening was performed to determine the presence of a germline mutation in the SMAD4, PTEN, and ENG genes in both patients. All coding exons and the flanking intronic regions of the SMAD4, PTEN, and ENG genes were amplified by polymerase chain reaction on a thermal cycler (Applied Biosystems, Foster City, CA, USA) using primer pairs designed by the authors. Direct sequencing was performed using the same primers on the ABI Prism 3130 Genetic Analyzer using the BigDye Terminator Cycle Sequencing Reaction Kit (Applied Biosystems). The sequences were analyzed using the Sequencher program (Gene Codes Corp., Ann Arbor, MI, USA) and compared with the reference sequence. The direct sequencing analysis revealed a novel nonsense mutation in the SMAD4 gene in both the mother and the son. The mutation, a C to G transition at position 1239 in exon 10, resulted in premature stop codon at tyrosine 413 (p.Tyr413*) (). To our knowledge, this mutation has not been described previously. The mutation was not detected in the PTEN and ENG genes.