Clin Genet 2012 Printed in Singapore. All rights reserved  2012 John Wiley & Sons A/S CLINICAL GENETICS doi: 10.1111/j.1399-0004.2012.01928.x Short Report Large deletions and splicing-site mutations in the STK11 gene in Peutz-Jeghers Chilean families Orellana P, L´ opez-K¨ ostner F, Heine C, Suazo C, Pinto E, Church J, Carvallo P, Alvarez K. Large deletions and splicing-site mutations in the STK11 gene in Peutz-Jeghers Chilean families. Clin Genet 2012.  John Wiley & Sons A/S, 2012 Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by mucocutaneous melanocytic macules, gastrointestinal hamartomatous polyposis and an increased risk of various neoplasms. Germline mutations in the serine/threonine kinase 11 (STK11 ) gene have been identified as a cause for PJS. The aim of this study was to characterize the genotype of Chilean PJS patients. Mutation screening of 13 patients from eight PJS families was performed using a single strand conformation polymorphism analysis, DNA sequencing and multiplex ligation-dependent probe amplification assay. The breakpoints of the genomic rearrangements were assessed by a long-range polymerase chain reaction and sequencing. The results revealed the existence of seven different pathogenic mutations in STK11 gene in seven unrelated families, including three point mutations and four large genomic deletions. Three of these point mutations (43%, 3/7) may be considered as novel. Our results showed that a germline mutation is present in STK11 in 88% of probands fulfilling the diagnostic criteria of PJS. In this study, the combination of two different experimental approaches in the screening of the STK11 in PJS, led to a higher percentage of mutation detection. Conflict of interest The authors declare no conflict of interest. P Orellana a , FL´ opez-K ¨ ostner a , C Heine a , C Suazo a , E Pinto a , J Church b , P Carvallo c and K Alvarez a a Laboratorio de Oncología y Gen ´ etica Molecular, Unidad de Coloproctología, Clínica Las Condes, Santiago, Chile, b Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA, and c Departamento de Biología Celular y Molecular, Facultad de Ciencias Biol ´ ogicas, Pontificia Universidad Cat ´ olica de Chile, Santiago, Chile Key words: germline mutation – hereditary colorectal cancer – Peutz-Jeghers Syndrome (PJS) – serine-threonine protein kinase (STK11) Corresponding author: Karin Alvarez, MSc, PhD, Laboratorio de Oncología y Gen ´ etica Molecular, Unidad de Coloproctología, Clínica Las Condes, Lo Fontecilla 441, Las Condes, Santiago, Chile. Tel.: +56 2 6108524; fax: +56 2 6104776; e-mail: kalvarez@clc.cl Received 22 March 2012, revised and accepted for publication 3 July 2012 Peutz-Jeghers Syndrome (PJS, MIM 175200) is a rare autosomal dominant inherited disorder with nearly complete penetrance, characterized by the presence of mucocutaneous pigmentation and gastrointestinal hamartomatous polyps. The main disadvantage of hamartomatous polyps is intussusception, which may result in intestinal obstruction, bleeding, and anemia. In addition, patients are susceptible to develop cancer in several organs such as colon, stomach, small bowel, pancreas, breast, ovary, testis and kidney. The mean age at diagnosis for these associated cancers is between 42 and 45 years, raising the cumulative cancer risk to 76% at age 70 (1). Germline mutations in the serine-threonine kinase 11 (STK11 ) gene have been identified as a cause for PJS (2, 3). This enzyme is a tumor suppressor gene that controls the growth of tumor cells and participates in apoptosis through its interaction with p53 (4, 5). STK11 mutations have been detected in 75% of PJS patients, analyzed by gene sequencing and multiplex ligation-dependent probe amplification (MLPA) (6–9). In these studies, point mutations correspond to the majority of the gene alterations (69%), followed by major gene rearrangements (31%). Different populations worldwide have been studied until today, however, data from Latin-American countries remain unknown. There is only one report from Colombia describing two mutations in PJS families (10). The aim of this study was to characterize the STK11 in Chilean families diagnosed with PJS, 1