Digestive Diseases and Sciences

, Volume 52, Issue 8, pp 1924–1933 | Cite as

Molecular and Clinical Characteristics in 46 Families Affected with Peutz–Jeghers Syndrome

  • Hamid Mehenni
  • Nicoletta Resta
  • Ginevra Guanti
  • Louisa Mota-Vieira
  • Aaron Lerner
  • Mohammed Peyman
  • Kim A. Chong
  • Larbi Aissa
  • Ali Ince
  • Angel Cosme
  • Michael C. Costanza
  • Colette Rossier
  • Uppala Radhakrishna
  • Randall W. Burt
  • Didier Picard
Original Article


Germline mutations of the tumor suppressor gene LKB1/STK11 are responsible for the Peutz–Jeghers syndrome (PJS), an autosomal-dominant disorder characterized by mucocutaneous pigmentation, hamartomatous polyps, and an increased risk of associated malignancies. In this study, we assessed the presence of pathogenic mutations in the LKB1/STK11 gene in 46 unrelated PJS families, and also carried genotype–phenotype correlation in regard of the development of cancer in 170 PJS patients belonging to these families. All LKB1/STK11 variants detected with single-strand conformational polymorphism were confirmed by direct sequencing, and those without LKB1/STK11 mutation were further submitted to Southern blot analysis for detection of deletions/rearrangements. Statistical analysis for genotype–phenotype correlation was performed. In 59% (27/46) of unrelated PJS cases, pathogenic mutations in the LKB1/STK11 gene, including 9 novel mutations, were identified. The new mutations were 2 splice site deletion–insertions, 2 missenses, 1 nonsense, and 4 abnormal splice sites. Genotype–phenotype analysis did not yield any significant differences between patients carrying mutations in LKB1/STK11 versus those without mutations, even with respect to primary biliary adenocarcinoma. This study presents the molecular characterization and cancer occurrence of a large cohort of PJS patients, increases the mutational spectrum of LKB1/STK11 allelic variants worldwide, and provides a new insight useful for clinical diagnosis and genetic counseling of PJS families.


Cancer Genotype–phenotype analysis Pathogenic LKB1/STK11 gene mutations Peutz–Jeghers syndrome 


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Hamid Mehenni
    • 1
    • 14
  • Nicoletta Resta
    • 2
  • Ginevra Guanti
    • 2
  • Louisa Mota-Vieira
    • 3
  • Aaron Lerner
    • 4
  • Mohammed Peyman
    • 5
  • Kim A. Chong
    • 6
  • Larbi Aissa
    • 7
  • Ali Ince
    • 8
  • Angel Cosme
    • 9
  • Michael C. Costanza
    • 10
  • Colette Rossier
    • 11
  • Uppala Radhakrishna
    • 12
  • Randall W. Burt
    • 13
  • Didier Picard
    • 1
  1. 1.Unité de Gastroentérologie & Hépatologie, Centre Médico-Chirurgical Rond-Point-Plainpalais et Département de biologie cellulaire, Unité de recherche des maladies prédisposant aux cancers gastro-intestinauxUniversité de GenèveGenèveSwitzerland
  2. 2.Sezione di Genetica Medica Dip. di Biomedicina dell’Età EvolutivaUniversità di BariBariItaly
  3. 3.Unidade de Genética e Patologia MolecularesHospital De Ponta DelgadaPonta DelgadaPortugal
  4. 4.Department of PediatricsHaifa HospitalHaifaIsrael
  5. 5.Shariati Hospital and Islamic Azad University of NajafabadNajafabadIran
  6. 6.Instituto da CriançaHospital das Clinicas da faculdade de medicina da Universidade de Sao PauloSao PauloBrazil
  7. 7.Service de chirurgie generaleCHU Ibn-RochdCasablancaMorocco
  8. 8.Gastroenterology ClinicHaydarpasa Numune Education and Training HospitalIstanbulTurkey
  9. 9.Servicio de DigestivoHospital DonostiaSan SebastianSpain
  10. 10.Division of Clinical EpidemiologyGeneva University HospitalsGenevaSwitzerland
  11. 11.Department of Genetic Medicine and DevelopmentUniversity of Geneva Medical School and University HospitalsGenevaSwitzerland
  12. 12.Green Cross Blood Bank & Genetic Research CentrePaldiIndia
  13. 13.Department of MedicineUniversity of Utah School of MedicineSalt Lake CityUtah
  14. 14.Centre Medical du Rond-point de PlainpalaisUnité de Gastroentérologie & HépatologieGenèveSwitzerland

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