Research On STK11Gene Coding Region Mutation Of Patients With Peutz-Jeghers Syndrome

Peutz-Jeghers syndrome is an unusual autosomal dominant inherited disorder characterized by multiple gastrointestinal hamartomatous and mucocutaneous pigmentation and by an increased risk for multi-organ cancer. The germline mutation of the STK11gene, located at chromosome19p13.3, is mainly responsible for the Peutz-Jeghers syndrome. STK11gene, as a tumor supressor, encodes a serine-threonine kinase. However, there may be some additional unknown mutation sites associated with this disease. This study aims to explore the sequence of STK11gene coding regions of patients with Peutz-Jeghers syndrome and identify mutational sites where STK11gene may exist. Meanwhile, the correlations of genotype-phenotype through combination of clinical characteristics will be investigated.In this study, the clinical data and blood samples were collected from49inpatients with Peutz-Jeghers syndrome in the Air-force General Hospital from January2010to June2011. The sequence of STK11gene coding regions was detected by PCR and DNA sequencing, and comparison of the normal sequence of STK11gene for analysis. In addition, their clinical datas were analyzed retrospectively, as well as the exploration of the relationship with the revevant genotype.The study revealed that there were21different mutations in the coding region of the STK11gene among29patients with Peutz-Jeghers syndrome, which contained10novel mutation sites, and3patients carried two mutational points. Family history-positive patients were earlier than family history-negative ones in the time of onset of gastrointestinal symptoms(P<0.05). It showed no significant difference in the time onset of surgery intervention due to major polyps between the familial positive and negative patients(P>0.05). Individuals with truncating mutations of STK11obviously had a earlier time to the onset of gastrointestinal symptoms compared with those individuals either with missense mutation or no detectable mutation(P<0.05), while there were no significant differences in the time of onset of surgery intervention due to major polyps among the patients with a truncating mutation, missense mutations and no detectable mutation(P>0.05).Mutations of STK11gene are major responsible for Peutz-Jeghers syndrome, and these novel mutations would greatly enlarge Human Gene Mutation Data, and lay the foundation for a further explanation of the molecular mechanism of Peutz-Jeghers syndrome. Moreover, surveillance should be done from as early as8years old and11years old respectively in the patients with a positive family history and/or truncating mutations patients to avoid complications.