title: Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.
abstract: 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.
authors.affiliation: Department of Neuroimmunology, Max-Planck-Institute of Psychiatry, Martinsried, Germany. djenne@alf.biochem.mpg.de
authors.forename: D E
authors.initials: DE
authors.lastname: Jenne
authors.forename: H
authors.initials: H
authors.lastname: Reimann
authors.forename: J
authors.initials: J
authors.lastname: Nezu
authors.forename: W
authors.initials: W
authors.lastname: Friedel
authors.forename: S
authors.initials: S
authors.lastname: Loff
authors.forename: R
authors.initials: R
authors.lastname: Jeschke
authors.forename: O
authors.initials: O
authors.lastname: Müller
authors.forename: W
authors.initials: W
authors.lastname: Back
authors.forename: M
authors.initials: M
authors.lastname: Zimmer
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002888:Chromosomes, Human, Pair 19; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010580:Peutz-Jeghers Syndrome / Q000201:enzymology* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases