title: A novel mutation in the STK11 gene causes heritable Peutz-Jeghers syndrome - a case report.
abstract: BACKGROUND
  Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. STK11 has been identified as a causative gene for this disease.
  
  
  METHODS
  Herein we report a Chinese Han kindred with PJS. Onset for the PJS signs in three of the patients was rarely as early as at birth. We identified a novel heterozygous mutation (c.440_441delGT, p.Arg147Leufs*15) in the gene STK11, causing a short frameshift followed by a deletion of 63% of the amino acids in the STK protein. This mutation co-segregated with the PJS phenotype, and was absent in two hundred of unrelated ethnicity-matched controls. The mutation led to expression decrease of unaffected STK11 protein in patients than in controls, as well in PJ polyps than in circulating leucocytes from the patients. Phosphorylation levels of the downstream kinase AMPKα altered according with the expression of STK11. These results indicated the possibility that haploinsufficiency and epigenetic reduction of STK11 contributed to the pathogenesis of the disease.
  
  
  CONCLUSIONS
  This study identifies a novel mutation in the pathogenic gene STK11 leading to PJS.
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan 2 Road, Guangzhou, 510080, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, the First Affiliated Hospital of Guangdong Medical University, Guangzhou, Guangdong, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan 2 Road, Guangzhou, 510080, China.|Guangzhou Forensic Science Institute, Guangdong Provincial Key Laboratory of Forensic Genetics, Guangzhou, Guangdong, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan 2 Road, Guangzhou, 510080, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan 2 Road, Guangzhou, 510080, China.
authors.forename: Shuang-Bo
authors.initials: SB
authors.lastname: Tang
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan 2 Road, Guangzhou, 510080, China. chengjd@mail.sysu.edu.cn.
authors.forename: Jian-Ding
authors.initials: JD
authors.lastname: Cheng
authors.affiliation: Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan 2 Road, Guangzhou, 510080, China. huangerw@mail.sysu.edu.cn.
authors.forename: Er-Wen
authors.initials: EW
authors.lastname: Huang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D005091:Exons; D016368:Frameshift Mutation; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010580:Peutz-Jeghers Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
keywords: Case report; Frameshift mutation; Peutz-Jeghers syndrome; STK11; Truncating mutation