A novel mutation in STK11 gene is associated with Peutz-Jeghers Syndrome in Chinese patients

Blood samples were collected from two unrelated Chinese PJS families totaling 20 individuals (9 male and 11 females), including 6 PJS patients. The entire coding region of the STK11 gene was amplified by polymerase chain reaction and analyzed by direct sequencing.A novel mutation, c.904C > T, in exon 7 was identified in both families. A C > T substitution changed codon 302 from CAG (glutamine) to TAG (stop), truncating the STK11 protein, thus leading to the partial loss of the kinase domain and complete loss of the α-helix C-terminus. Furthermore, one PJS patient from each family was diagnosed with a visceral cancer, a colon cancer and a liver cancer respectively.We predict that this novel mutation, p.Q302X, is most likely responsible for development of the PJS phenotype and may even contribute to malignancy.Peutz-Jeghers Syndrome (PJS; MIM#175200) is a rare autosomal dominant disorder characterized by gastrointestinal hamartomatous polyps, mucocutaneous pigmentation, and an increased risk for the development of gastrointestinal (GI) and various extra-GI malignancies [1,2]. The relative cancer risk has been estimated to be 9-18 times higher in PJS patients than the general population [3,4].Mutations in the serine-threonine kinase 11 (STK11/LKB1, MIM#602216) gene on chromosome 19p13.3 have been considered to be the major cause of PJS [5,6]. The gene is divided into nine exons that encode a 433 amino acid protein, which acts as a tumour suppressor. Mutation detection rates of 10-94% have been achieved at different centers, depending on the screening method, with considerable uncharacterized genetic heterogeneity remaining in this syndrome [2,7]. Most mutations are frameshift or nonsense changes, which result in an abnormal truncated protein and the consequent loss of kinase activity [8]. However, the STK11 mutation spectrum and genotype-phenotype correlation are still poorly understood.Here, we report a novel nonsense mutation, c.904C > T (p.Q302X), in exon 7 from two