Abstract 2645: Genomic deletions and point mutations in the STK11 gene in Peutz-Jeghers Chilean families

Abstract

Abstract Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis. Individuals with PJS are at increased risk for development of various neoplasms. The genetic susceptibility for PJS has been associated with germline mutation in the serine/threonine kinase 11 (STK11) gene. The aim of the present study was to characterize the genotype and phenotype of Chilean PJS patients. Methods: Mutation screening of 13 patients from 8 PJS families was performed by using single strand conformation polymorphism (SSCP) analysis and DNA sequencing, covering the entire coding region and the splice-site boundaries. In addition, multiplex ligation-dependent probe amplification (MLPA) assay was used for the identification of large exonic deletions or duplications. Results: We identified seven different pathogenic mutations in STK11 gene in 7 unrelated families. Point mutations correspond to a small deletion (c.109delC) in exon 1 that generates a premature stop codon and two intronic mutations localized in splice site of intron 4 (c.597+2 T>A) and intron 6 (c.862-2 A>G). The pathogenic effect on splicing of intronic changes was demonstrated in mRNA of STK11 from lymphocytes of patients. By MLPA, we identified four large deletions ranging from one exon to the whole gene. Breakpoints were identified in two of these patients. Three point mutations (43%, 3/7) may be considered as novel. Conclusions: Different germline mutations in STK11 were detected. A combination of sensitive techniques may improve a high STK11 mutation detection frequency (88%) in PJS Chilean families. Funded by Clinica Las Condes Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2645. doi:1538-7445.AM2012-2645