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J Med Genet 1999;36:365-368 doi:10.1136/jmg.36.5.365
  • Original article

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

  1. Z-J Wanga,b,
  2. M Churchmana,
  3. E Avizienytec,
  4. C McKeownd,
  5. S Daviese,
  6. D G R Evansf,
  7. A Fergusong,
  8. I Ellish,
  9. Wen-Huai Xub,
  10. Zhong-Yu Yanb,
  11. L A Aaltonenc,
  12. I P M Tomlinsona,i
  1. aTumour Genetics Group, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK, bDepartment of Surgery, The First School of Medicine, Beijing University of Medicine, Beijing, China, cDepartment of Medical Genetics, University of Helsinki, Haartman Institute, Haartmaninkatu 3, PO Box 21, Fin-00014, Helsinki, Finland, dDepartment of Clinical Genetics, Birmingham Women’s Hospital, Edgbaston, Birmingham B15 2TG, UK, eInstitute of Medical Genetics, University Hospital of Wales, Heath Park, Cardiff CF4 4XN, UK, fDepartment of Clinical Genetics, St Mary’s Hospital, Manchester M13 0JH, UK, gDepartment of Gastroenterology, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK, hDepartment of Clinical Genetics, Royal Liverpool Children’s Hospital, Liverpool L12 2AP, UK, iMolecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK
  1. Dr Tomlinson, London.
  • Received 6 November 1998
  • Revised 25 January 1999

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.

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