Study On The Mutations Of STK11 Gene In Peutz-Jeghers Syndrome

Background: Peutz-Jeghers syndrome(PJS, OMIM 175200) is a rare, autosomal dominant genetic disease, which is characterized by mucocutaneous pigmentations and gastrointestinal polyposis. It is also called perioral pigmentation-intestinal polyposis syndrome. And the pathological types of most polyposis are adenoma and hamartoma. The gastrointestinal polyps may cause gastrointestinal bleeding, anaemia and abdominal pain due to intussusception, obstruction or infarction. PJS increases frequency of gastrointestinal and extraintestinal malignancies. It is generally accepted that PJS is caused by germ-line mutations in the STK11(LKB1) gene which is located at chromosome 19p13.3 that encodes the serine/threonine kinase and acts as a tumor suppressor by regulating cell proliferation, polarity, functions and energy metabolism in a variety of malignant tumors. De novo mutations of STK11 gene are discovered and reported steadily and ceaselessly, which not only expand mutation spectrum of STK11 gene, but also lay the foundation for the research on the relationship between phenotype and genotype in PJS. In the study, three families and two sporadic cases were collected and made a definite diagnosis of PJS. And the DNA direct sequencing was used to detect mutations of STK11 gene in these cases.Objective: To identify novel pathogenicity mutations of the STK11 gene in three pedigrees and two sporadic cases with Peutz-Jeghers Syndrome(PJS).Methods: We collected blood samples and clinical data from the pedigrees and the sporadic cases with PJS. And we extracted genomic DNA from the peripheral blood of these patients. The coding exons and flanking sequences of STK11 gene were amplified by using polymerase chain reaction(PCR). The products of PCR were analyzed by DNA direct sequencing to detect mutations in these cases.Results: Two novel heterozygous missense mutations were presented in two Chinese PJS families. One mutatin c.908T>G(p.Ile303Ser) is in the exon 7 of STK11 gene of the family 1. And the other mutation c. 1251G>T(p.Ala417Ser) is in the exon 9 of STK11 gene of the family 2. The healthy members of these families were not found the corresponding mutatins and the same situation in 100 unrelated control individuals. Heterozygous 920+7G>C SNP in intron 7 of STK11 gene was detected in the first family and third family. And the sporadic patients were not found to have mutations in STK11 gene coding region.Conclusion: The data suggests that the two missense mutations, c.908T>G(p.Ile303Ser) and c.1251G>T(p.Ala417Ser) in the STK11 gene could be the underlying cause of the first and second PJS family and may result in malignant transformation. This study provides more mutation information of the STK11 gene and lays the root for genetic counseling, genetic diagnosis, prenatal diagnosis in these families with PJS in the future.