title: Exome sequencing revealed novel germline mutations in Chinese Peutz-Jeghers syndrome patients.
abstract: OBJECTIVE
  Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disorder which predisposes to the development of various cancers. Germline mutation in the serine/threonine kinase 11 gene (STK11) is known as one of the major causes of PJS. However, a notable proportion of PJS samples do not carry any mutation in STK11, suggesting possible genetic heterogeneity in the disease and the existence of other causative variants.
  
  
  RESULTS
  In order to identify other germline variants in the coding regions of the genome that are associated with PJS, we performed exome sequencing in three Chinese individuals with PJS and identified 16 common germline variants (12 protein-coding including STK11, 4 in pre-microRNAs). We further validated protein-coding variants in six PJS individuals (three with wild-type STK11) and predicted the functional impact. As result, we found that 7 coding variants are likely to have functional impacts. Especially, we identified 2 new germline variants which are represented in all six PJS samples and are independent of STK11 mutation.
  
  
  CONCLUSIONS
  Our study provided an exomic view of PJS. The germline variants identified in our analysis may help to resolve the complex genetic background of the disease and thus lead to the discovery of novel causative variants of PJS.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, 201 Hubin South Road, Xiamen, 361004, Fujian, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Wang
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Xie
authors.forename: Qi-Yuan
authors.initials: QY
authors.lastname: Li
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Hu
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Ren
authors.forename: Bayasi
authors.initials: B
authors.lastname: Guleng
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D000328:Adult; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010580:Peutz-Jeghers Syndrome / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases