Exome Sequencing Revealed Novel Germline Mutations In Chinese Peutz-Jeghers Syndrome Patients

Background Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disorder andpredisposes to various neoplasms. Germline mutations in the serine/threonine kinase11(STK11) genes have been identified as a major cause of PJS. However a notableproportion of PJS genealogy and sporadic samples carrying wild type of STK11suggests that STK11mutation is not the only cause of PJS and that uncharacterizedcausative genetic heterogeneity may exist.Result In order to identify novel genetic variants associated to PJS, we performedexome sequencing in three Chinese individuals with PJS from a two-generationfamily (father, daughter, son) and further verified the variants using Sangersequencing. we identified eight common mutations in the protein-coding regions ofeight genes (including STK11) and four mutations in four pre-microRNAs. We usedSIFT to predict functional impact of these variants. As result, we found that seven ofvariants in genes were to be functionally damaging. Especially, the mutation ofSTK11, C.341-342T in exon2, resulting in a frameshift (p.V114fs) is a novel variantand has not been previously described.Conclusion our study provided an exome-wide view of the genetic heterogeneity ofPJS. The mutations found in our analysis have expanded the genotypic spectrum ofSTK11variants, and may lead to discovery of novel causative mutations in PJS.