| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
a Tumour Genetics
Group, Nuffield Department of Clinical Medicine, University of Oxford,
John Radcliffe Hospital, Oxford OX3 9DU, UK, b Department of
Surgery, The First School of Medicine, Beijing University of Medicine,
Beijing, China, c Department of Medical Genetics, University of
Helsinki, Haartman Institute, Haartmaninkatu 3, PO Box 21, Fin-00014, Helsinki, Finland, d Department
of Clinical Genetics, Birmingham Women's Hospital, Edgbaston,
Birmingham B15 2TG, UK, e Institute of Medical Genetics, University
Hospital of Wales, Heath Park, Cardiff CF4 4XN, UK, f Department of Clinical Genetics, St Mary's
Hospital, Manchester M13 0JH, UK, g Department of Gastroenterology, Western General
Hospital, Crewe Road, Edinburgh EH4 2XU, UK, h Department of Clinical Genetics, Royal Liverpool
Children's Hospital, Liverpool L12 2AP, UK, i Molecular
and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
Correspondence to: Dr Tomlinson, London.
Received 6 November 1998;
Revised version accepted for publication 25 January 1999
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.
This article has been cited by other articles:
|
|
 |
|
  N Hearle, V Schumacher, F H Menko, S Olschwang, L A Boardman, J J P Gille, J J Keller, A M Westerman, R J Scott, W Lim, et al. STK11 status and intussusception risk in Peutz-Jeghers syndrome. J. Med. Genet., August 1, 2006; 43(8): e41 - e41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Volikos, J Robinson, K Aittomaki, J-P Mecklin, H Jarvinen, A M Westerman, F W M de Rooji, T Vogel, G Moeslein, V Launonen, et al. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J. Med. Genet., May 1, 2006; 43(5): e18 - e18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Schumacher, T Vogel, B Leube, C Driemel, T Goecke, G Moslein, and B Royer-Pokora STK11 genotyping and cancer risk in Peutz-Jeghers syndrome J. Med. Genet., May 1, 2005; 42(5): 428 - 435. [Full Text] [PDF]
|
|
|
|
|
|
S. Olschwang, C. Boisson, and G. Thomas Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma J. Med. Genet., June 1, 2001; 38(6): 356 - 360. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
