title: Novel and recurrent mutations of STK11 gene in six Chinese cases with Peutz-Jeghers syndrome.
abstract: BACKGROUND
  The serine/threonine kinase 11 (STK11) gene is the main causal gene in Peutz-Jeghers syndrome (PJS). Abnormal STK11 may increase cancer risk of PJS patients via affecting its target proteins such as P53, AMPK, and PTEN. In this study, we investigated the molecular basis of six Chinese PJS patients.
  
  
  METHODS
  Blood samples were collected from four Chinese PJS families and two sporadic patients. The entire coding region of the STK11 gene was amplified by polymerase chain reaction and analyzed by direct sequencing. Functions of mutants were assessed by PolyPhen-2, Swiss-Model software, and luciferase reporter assay.
  
  
  RESULTS
  Novel mutations (c.842_843insC, c.804_805insG, and c.922T>G) and recurrent mutations (c.526G>A, c.180C>G, and c.1062C>G) were identified. Missense mutation c.922T>G and c.526G>A were predicted as probably damaging by PolyPhen-2, while c.1062C>G was benign. Mutation c.108C>G was a nonsense mutation. The 284Ter mutants of c.842_843insC and c.804_805insG significantly diminished the capacity of P53 activity in 293FT cells.
  
  
  CONCLUSIONS
  Our results support that STK11 gene mutations underlie Chinese patients with PJS. Mutation involving partial kinase domain disrupts normal function of STK11. Our results also enlarge the spectrum of STK11 variants in PJS patients.
authors.affiliation: Department of Medical Genetics, College of Basic Medical Science, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Limeng
authors.initials: L
authors.lastname: Dai
authors.forename: Liyuan
authors.initials: L
authors.lastname: Fu
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Meng
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Xingying
authors.initials: X
authors.lastname: Guan
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D044466:Asian People; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D010580:Peutz-Jeghers Syndrome / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D055815:Young Adult
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases