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No TGFBRII germline mutations in juvenile polyposis patients without SMAD4 or BMPR1A mutation
  1. L A A Brosens1,
  2. W A van Hattem1,2,
  3. M C E Kools1,
  4. C Ezendam1,
  5. F H Morsink1,
  6. W W J de Leng1,
  7. F M Giardiello3,
  8. G J A Offerhaus1,2,4
  1. 1
    Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2
    Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
  3. 3
    Department of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  4. 4
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  1. Dr L A A Brosens, Department of Pathology (H04-312), University Medical Center Utrecht, Postbox 85500, 3508 GA Utrecht, The Netherlands; L.A.A.Brosens{at}

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Juvenile polyposis (JPS) is an autosomal dominant disorder characterised by the presence of multiple gastro-intestinal juvenile polyps and an increased risk of colorectal cancer (CRC).1 JPS is caused by germline mutation of SMAD4 or BMPR1A, both involved in the transforming growth factor β/bone morphogenic protein (TGFβ/BMP) signalling pathway. A recent study by van Hattem et al, published in this journal (Gut 2008;57:623–7), showed that a germline defect in one of these genes is found in approximately 50% of JPS patients, with 30–40% being a point mutation or small deletion and 10–15% a large genomic deletion. Since no germline defect is found in ∼50% of JPS patients, it is likely that other genes exist which cause JPS.2

Several candidate genes, mostly involved in TGFβ/BMP signalling, have been investigated for a role in JPS pathogenesis. No mutations have been found in these genes.36 (table 1) Recently, the TGFβ co-receptor endoglin was proposed as a JPS susceptibility gene, but other studies could …

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  • Funding: Supported by The Netherlands Digestive Disease Foundation (MLDS WS 04–06), The John G. Rangos, Sr. Charitable Foundation, The Clayton Fund, and NIH grants CA 53801, 63721, 51085, and P50 CA 93-16. The study sponsors were not involved in study design, collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication.

  • Competing interests: None.

  • Ethics approval: Ethics approval was granted by the Johns Hopkins Institutional Review Board on 28 September 2007. The study was carried out in accordance with the ethical guidelines of the research review committees of the institutions in Amsterdam and Utrecht.