RT Journal Article
SR Electronic
T1 Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 365
OP 368
DO 10.1136/jmg.36.5.365
VO 36
IS 5
A1 Wang, Z-J
A1 Churchman, M
A1 Avizienyte, E
A1 McKeown, C
A1 Davies, S
A1 Evans, D G R
A1 Ferguson, A
A1 Ellis, I
A1 Xu, Wen-Huai
A1 Yan, Zhong-Yu
A1 Aaltonen, L A
A1 Tomlinson, I P M
YR 1999
UL http://jmg.bmj.com/content/36/5/365.abstract
AB 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.