Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients

Germline mutations of the LKB1 (STK11) serine/threonine kinase gene (chromo some 19p13.3) cause Peutz-Jeghers syndrome, which is characterised by hamar tomas 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 ger mline LKB1 mutations by DNA sequencing in 12 Peutz-Jeghers patients (three sporadic and nine familial cases). Mutations were found in seven (58%) case s, in exons 1, 2, 4, 6, and 9. Five of these mutations, two of which are id entical, are predicted to lead to a truncated protein (three frameshifts, t wo nonsense changes). A further mutation is an in frame deletion of 6 bp, r esulting in a deletion of lysine and asparagine; the second of these amino acids is conserved between species. The seventh mutation is a missense chan ge 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 cli nical features, predictive and diagnostic testing for LKB1 mutations will b e useful for selected patients in both familial and non-familial contexts.