Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Muller O, Back W, Zimmer MPeutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18: 38-43

Department of Neuroimmunology, Max-Planck-Institute of Psychiatry, Martinsried, Germany.
Nature Genetics (Impact Factor: 29.35). 02/1998; 18(1):38-43. DOI: 10.1038/ng0198-38
Source: PubMed


Peutz-Jeghers (PJ) syndrome is an autosomal-dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. The PJ gene was recently mapped to chromosome 19p13.3 by linkage analysis, with the highest lod score at marker D19S886. In a distance of 190 kb proximal to D19S886, we identified and characterized a novel human gene encoding the serine threonine kinase STK11. In a three-generation PJ family, we found an STK11 allele with a deletion of exons 4 and 5 and an inversion of exons 6 and 7 segregating with the disease. Sequence analysis of STK11 exons in four unrelated PJ patients has identified three nonsense and one acceptor splice site mutations. All five germline mutations are predicted to disrupt the function of the kinase domain. We conclude that germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, cause the manifestations of PJ syndrome.

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Available from: W. Back, Apr 23, 2014
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    • "Mutations in the serine-threonine kinase 11 (STK11/LKB1) gene on chromosome 19p13.3 are considered the major cause of PJS [2]. Germline mutations of STK11 are documented in up to 70%-80% of patients with PJS and up to 15% of cases have deletions of all or part of STK11 [3]. "
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    ABSTRACT: Peutz-Jeghers syndrome (PJS), also known as periorificial lentiginosis, is a rare autosomal dominant inherited disease with an incidence of 1/200,000 live-borns. Mutations in the serine-threonine kinase 11 (STK11) gene are considered the major cause of PJS. The most frequent complication at young age is recurrent intussusception due to multiple hamartomatous polyps, primarily in the small intestine. Although extremely rare, the small bowel should be fully examined to be certain additional intussusceptions are not present. Herein, we report on a case of PJS with germline mutation of STK11 in a 12-year-old young girl who presented as a rare case of two small intestinal intussusceptions and review the literature.
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    • "These infrequently mutated genes provide further insight into cellular pathways altered in PDAC, as well as potential therapeutic targets for gene-specific therapies (Maitra et al., 2006). The STK11/LKB1 gene on chromosome 19p13 encodes for a serine/threonine kinase that regulates cell polarity and metabolism (Jenne et al., 1998; Schneider and Schmid, 2003; Hezel et al., 2006). Inactivation of the STK11 gene appears to play a role in both hereditary and sporadic PDAC (Schneider and Schmid, 2003; Hezel et al., 2006). "
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    • "Amos et al confirmed this finding (14). The STK11 gene was known to be present on chromosome 19 (15,16) and Yoon et al subsequently identified a number of mutation types in this gene, including missense, frame shift, nonsense and splicing site mutations, in 10 PJS patients using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP; Fig. 1) (17). Germline mutations were present in five of these patients. "
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    ABSTRACT: Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.
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