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Genotype–phenotype correlations in Peutz-Jeghers syndrome
  1. C I Amos1,
  2. M B Keitheri-Cheteri1,
  3. M Sabripour1,
  4. C Wei1,
  5. T J McGarrity2,
  6. M F Seldin3,
  7. L Nations1,
  8. P M Lynch4,
  9. H H Fidder5,
  10. E Friedman6,
  11. M L Frazier1
  1. 1Department of Epidemiology, U.T. M.D. Anderson Cancer Center HMB, Houston, TX, USA
  2. 2Division of Gastroenterology and Hepatology, Penn State College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA
  3. 3Rowe Program in Genetics, UC Davis, CA, USA
  4. 4Department of GI Medicine and Nutrition, U.T. M.D. Anderson Cancer Center HMB, Houston, TX, USA
  5. 5Institute of Gastroenterology, Sheba Medical Center, Tel-Hashomer, 52621, Israel
  6. 6The Susanne Levy Gerner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, 52621, Israel
  1. Correspondence to:
 C Amos PhD
 Box 189, Department of Epidemiology, The University of Texas U.T. M.D. Anderson Cancer Center, 1515 Holcombe Boulevard Houston, TX 77030, USA;


Background and aims: Peutz-Jeghers syndrome (PJS) is a dominantly inherited disorder often caused by mutations in STK11. Time to onset of symptoms was characterised for a large collection of individuals with PJS who had been tested for STK11 mutations and genotype–phenotype correlations were evaluated.

Methods: We characterised mutations in 42 independent probands and also used a historical cohort design to study 51 individuals with Peutz-Jeghers syndrome who had completed self-administered questionnaires.

Results: Mutations were detected in 22/32 (69%) probands with PJS and 0/10 probands referred to rule out PJS. Real-time PCR analysis to quantitate DNA failed to detect any large deletions in PJS participants without STK11 mutations. The median time to onset for gastrointestinal symptoms or polypectomy was 13 years of age but showed a wide variability. Gastric polyps were frequent in PJS participants, with a median age at onset of 16 years. Individuals with missense mutations had a significantly later time to onset of first polypectomy (p = 0.04) and of other symptoms compared with those participants either with truncating mutations or no detectable mutation.

Conclusion: STK11 mutation analysis should be restricted to individuals who meet PJS criteria or their close relatives. Direct sequencing of STK11 yields a high rate of point mutations in individuals who meet phenotypic PJS criteria. Individuals with missense mutations of STK11 typically had a later time to onset for PJS symptoms. The common occurrence of gastric polyps may facilitate chemopreventive studies for this disorder.

  • mutation analysis
  • Peutz-Jeghers syndrome
  • polyps
  • STK11
  • time to onset
  • GI, gastrointestinal
  • PJS, Peutz-Jeghers syndrome

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  • This research has been partially supported by grants ACS/RPG99-030-01-CCE-3 and NIH/NCI CA78142.

  • Conflicts of interest: none declared.