title: Novel serine/threonine kinase 11 gene mutations in Peutz-Jeghers syndrome patients and endoscopic management.
abstract: OBJECTIVE
  To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps.
  
  
  METHODS
  Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had hamartomatous polyposis in the gastrointestinal tract, including the small intestine, along with mucocutaneous hyperpigmentation. Narrow-band imaging (NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions. NBI magnification findings could be classified into three groups (type A, type B, or type C). Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy. Genomic DNA was extracted from a whole blood sample from each subject. All of the coding exons of STK11 gene, its boundary regions, and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction, and direct sequencing was performed to assess the germline mutations.
  
  
  RESULTS
  NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps. Overall, we found 5 cases of type A and one case without the examination for the gastric polyps, while there were 4 cases of type B and 2 case of type A for the colorectal polyps. Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications. The only delayed complication included the occurrence of bleeding in a case, and this was successfully managed with hemoclips. Resected polyps contained no malignant components. Based on mutation analysis, all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5, which resulted in the production of a truncated protein (Q220X). In Family II, a case had -252C>A and -193C>A in the promoter region. In Family III, a case was found to have the +1062C>G (F342L) mutation in exon 8.
  
  
  CONCLUSIONS
  We found two novel mutations of STK11 in association with PJS. Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.
authors.affiliation: Hiroyuki Yajima, Shigeru Kohno, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yajima
authors.forename: Hajime
authors.initials: H
authors.lastname: Isomoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishioka
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Ken
authors.initials: K
authors.lastname: Ohnita
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Fuminao
authors.initials: F
authors.lastname: Takeshima
authors.forename: Saburo
authors.initials: S
authors.lastname: Shikuwa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakao
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
keywords: Double-balloon enteroscopy; Gastrointestinal hamartomatous polyps; Narrow-band imaging; Peutz-Jeghers syndrome; Serine/threonine kinase 11