title: Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients.
abstract: Germline mutations of the LKB1 (STK11) serine/threonine kinase gene (chromosome 19p13.3) cause Peutz-Jeghers syndrome, which is characterised by hamartomas of the gastrointestinal tract and typical pigmentation. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population. Here, we report the results of a screen for germline LKB1 mutations by DNA sequencing in 12 Peutz-Jeghers patients (three sporadic and nine familial cases). Mutations were found in seven (58%) cases, in exons 1, 2, 4, 6, and 9. Five of these mutations, two of which are identical, are predicted to lead to a truncated protein (three frameshifts, two nonsense changes). A further mutation is an in frame deletion of 6 bp, resulting in a deletion of lysine and asparagine; the second of these amino acids is conserved between species. The seventh mutation is a missense change in exon 2, converting lysine to arginine, affecting non-conserved amino acids and of uncertain functional significance. Despite the fact that Peutz-Jeghers syndrome is usually an early onset disease with characteristic clinical features, predictive and diagnostic testing for LKB1 mutations will be useful for selected patients in both familial and non-familial contexts.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, UK.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Churchman
authors.forename: E
authors.initials: E
authors.lastname: Avizienyte
authors.forename: C
authors.initials: C
authors.lastname: McKeown
authors.forename: S
authors.initials: S
authors.lastname: Davies
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.forename: A
authors.initials: A
authors.lastname: Ferguson
authors.forename: I
authors.initials: I
authors.lastname: Ellis
authors.forename: W H
authors.initials: WH
authors.lastname: Xu
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Yan
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: I P
authors.initials: IP
authors.lastname: Tomlinson
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D010580:Peutz-Jeghers Syndrome / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases