BACKGROUND AND AIMS: 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. METHODS AND 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.
BACKGROUND AND AIMS: 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. METHODS AND 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: P Karuman; O Gozani; R D Odze; X C Zhou; H Zhu; R Shaw; T P Brien; C D Bozzuto; D Ooi; L C Cantley; J Yuan Journal: Mol Cell Date: 2001-06 Impact factor: 17.970
Authors: A M Westerman; M M Entius; P P Boor; R Koole; E de Baar; G J Offerhaus; J Lubinski; D Lindhout; D J Halley; F W de Rooij; J H Wilson Journal: Hum Mutat Date: 1999 Impact factor: 4.878
Authors: Pia Alhopuro; Denis Phichith; Sari Tuupanen; Heli Sammalkorpi; Miranda Nybondas; Juha Saharinen; James P Robinson; Zhaohui Yang; Li-Qiong Chen; Torben Orntoft; Jukka-Pekka Mecklin; Heikki Järvinen; Charis Eng; Gabriela Moeslein; Darryl Shibata; Richard S Houlston; Anneke Lucassen; Ian P M Tomlinson; Virpi Launonen; Ari Ristimäki; Diego Arango; Auli Karhu; H Lee Sweeney; Lauri A Aaltonen Journal: Proc Natl Acad Sci U S A Date: 2008-04-07 Impact factor: 11.205
Authors: L A Boardman; S N Thibodeau; D J Schaid; N M Lindor; S K McDonnell; L J Burgart; D A Ahlquist; K C Podratz; M Pittelkow; L C Hartmann Journal: Ann Intern Med Date: 1998-06-01 Impact factor: 25.391