Mutations in the STK11 gene in Czech Peutz-Jeghers families

Background: Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis. The germline mutations in the serine/threonine kinase 11 (STK11) gene have been shown to be associated with the disease. Individuals with PJS are at increased risk for various neoplasms. Molecular analysis could be helpful in disease management of PJS probands. Methods: We investigated the promotor and the entire coding region including the splice-site boundaries of the STK11 gene in genomic DNA of 8 individuals from five Czech families by sequencing analysis and multiplex ligation probe-dependent amplification (MLPA) assay. Results: One frameshift and two large deletions were found in 6 individuals from three families. One individual developed gastric and lung cancer. No other proband has developed carcinoma so far. Two patients with sporadic disease were not found to carry any germline variation of the STK11 gene. A familial case with very aggressive gastric carcinoma is described. Conclusion: We found germline mutations of the STK11 gene in probands fulfilling PJS diagnostic criteria. A sporadic case with hyperpigmentation and only one adenomatous polyp was also found to have a deletion of the whole STK11 gene. *Corresponding author: Peter Vasovčák, Institute of Biology and Genetics, Charles University, Medical School, V Úvalu 84, Prague 5, 150 06, Czech Republic. E-mail: [email protected]