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GermlineSMAD4 orBMPRIA mutations and phenotype of juvenile polyposis

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Abstract

Background

Juvenile polyposis (JP) is an inherited condition predisposing to upper gastrointestinal (UGI) polyps and colorectal cancer. Two genes are known to predisose to JP,SMAD4 and bone morphogenetic protein receptor type 1A (BMPR1A). The object of this study was to determine the differences in phenotype of patients withSMAD4 orBMPR1A mutations (MUT+) compared with those without (MUT-).

Methods

DNA was extracted from 54 JP probands and used for polymerase chain reaction of all exons ofSMAD4 andBMPRIA. Products were then sequenced and analyzed for mutations. Medical record data were used to create a JP database, and statistical analysis was performed using Fisher's exact and unpairedt-tests.

Results

Nine of 54 patients had germlineSMAD4 mutations, 13 hadBMPR1A mutations, and 32 had neither. There were no significant differences betweenSMAD4+ andBMPR1A+ cases in terms of clinical factors examined, except for a family history of UGI involvement (P<.01). There was a higher prevalence of familial cases in MUT+ patients (P=.09),>10 lower gastrointestinal polyps (P=.06), and frequency of family history of gastrointestinal cancer compared with MUT-patients (P=.01).

Conclusions

Patients with germlineSMAD4 orBMPR1A mutations have a more prominent JP phenotype than those without, andSMAD4 mutations predispose to UGI polyposis.

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Authors and Affiliations

  1. University of Iowa College of Medicine, Iowa City, Iowa

    M. G. Sayed MD, A. F. Ahmed MD, J. R. Ringold BS, M. E. Anderson BS, J. L. Bair BS, F. A. Mitros MD & J. R. Howe MD

  2. Creighton University, Omaha, Nebraska

    H. T. Lynch MD & S. T. Tinley RN, MS, CGC

  3. Mayo Clinic, Rochester, Minnesota

    G. M. Petersen PhD

  4. Johns Hopkins University, Baltimore, Maryland

    F. M. Giardiello MD & B. Vogelstein MD

Authors
  1. M. G. Sayed MD
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  2. A. F. Ahmed MD
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  3. J. R. Ringold BS
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  5. J. L. Bair BS
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  6. F. A. Mitros MD
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  7. H. T. Lynch MD
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  12. J. R. Howe MD
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Correspondence to J. R. Howe MD.

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Sayed, M.G., Ahmed, A.F., Ringold, J.R. et al. GermlineSMAD4 orBMPRIA mutations and phenotype of juvenile polyposis. Annals of Surgical Oncology 9, 901–906 (2002). https://doi.org/10.1007/BF02557528

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  • DOI: https://doi.org/10.1007/BF02557528

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