Germline mutation analysis of STK11 gene using direct sequencing and multiplex ligation-dependent probe amplification assay in Korean children with Peutz-Jeghers syndrome.

Background and Aims Peutz-Jeghers syndrome is an autosomal, dominantly inherited disease characterized by mucocutaneous hyperpigmentation and hamartomatous polyps of the gastrointestinal tract. In this study, mutation analysis of the STK11 gene was performed to establish the genetic background of Peutz-Jeghers syndrome in Korean children.Methods This study included 17 children who were diagnosed with Peutz-Jeghers syndrome based on clinical diagnostic criteria between July 2006 and December 2007.The clinical records of these children were reviewed retrospectively.Genomic DNA was extracted from the blood samples of each patient and used for direct sequencing and the MLPA (multiplex ligation-dependent probe amplification)assay.Results By direct sequencing, mutations in the STK11 gene were observed in five of 17 (29.4%) children with Peutz-Jeghers syndrome. Missense mutations were observed in four, and a frameshift mutation in one. All these mutations were present in the kinase domain of the STK11 gene. By MLPA analysis, mutations in the STK11 gene were observed in six (35.3%) children—exonic deletions were observed in five and exonic duplication in one. Conclusions The detection rate of STK11 gene mutations by direct sequencing is relatively low, even in children clinically diagnosed with Peutz-Jeghers syndrome. With the introduction of the MLPA assay as a new cytogenetic technique, large deletions and exonic duplications could also be detected in children with PJS. In the future, these results may be useful for the genetic diagnosis of Peutz-Jeghers syndrome in Korean children.