Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis

Ann Surg Oncol. 2002 Nov;9(9):901-6. doi: 10.1007/BF02557528.


Background: Juvenile polyposis (JP) is an inherited condition predisposing to upper gastrointestinal (UGI) polyps and colorectal cancer. Two genes are known to predispose 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 with SMAD4 or BMPR1A mutations (MUT+) compared with those without (MUT-).

Methods: DNA was extracted from 54 JP probands and used for polymerase chain reaction of all exons of SMAD4 and BMPR1A. 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 unpaired t-tests.

Results: Nine of 54 patients had germline SMAD4 mutations, 13 had BMPR1A mutations, and 32 had neither. There were no significant differences between SMAD4+ and BMPR1A+ 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 germline SMAD4 or BMPR1A mutations have a more prominent JP phenotype than those without, and SMAD4 mutations predispose to UGI polyposis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone Morphogenetic Protein Receptors, Type I
  • Child
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Genes, Tumor Suppressor*
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Intestinal Polyps / genetics*
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics*
  • Receptors, Growth Factor / genetics*
  • Smad4 Protein
  • Trans-Activators / genetics*


  • DNA-Binding Proteins
  • Receptors, Growth Factor
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • Protein Serine-Threonine Kinases
  • BMPR1A protein, human
  • Bone Morphogenetic Protein Receptors, Type I