Germline Mutations in the Polyposis-Associated Genes BMPR1A, SMAD4, PTEN, MUTYH and GREM1 Are Not Common in Individuals with Serrated Polyposis Syndrome

PLoS One. 2013 Jun 21;8(6):e66705. doi: 10.1371/journal.pone.0066705. Print 2013.


Background: Recent reports have observed that individuals with serrated polyps, some of whom meet the clinical diagnostic criteria for Serrated Polyposis Syndrome (SPS), are among those who carry germline mutations in genes associated with polyposis syndromes including; (1) genes known to underlie hamartomatous polyposes (SMAD4, BMPR1A, and PTEN), (2) MUTYH-associated polyposis and (3) GREM1 in Hereditary Mixed Polyposis Syndrome (HMPS). The aim of this study was to characterise individuals fulfilling the current WHO criteria for SPS for germline mutations in these polyposis-associated genes.

Methods: A total of 65 individuals with SPS (fulfilling WHO criteria 1 or 3), were recruited to the Genetics of Serrated Neoplasia study between 2000 and 2012, through multiple Genetics or Family Cancer Clinics within Australia, or from the New Zealand Familial Gastrointestinal Cancer Service. Individuals with SPS were tested for coding mutations and large deletions in the PTEN, SMAD4, and BMPR1A genes, for the MUTYH variants in exons 7 (Y179C) and 13 (G396D), and for the duplication upstream of GREM1.

Results: We found no variants that were likely to be deleterious germline mutations in the SPS cases in the PTEN, SMAD4, and BMPR1A genes. A novel variant in intron 2 (c.164+223T>C) of PTEN was identified in one individual and was predicted by in silico analysis to have no functional consequences. One further individual with SPS was found to be mono-allelic for the MUTYH G396D mutation. No individuals carried the recently reported duplication within GREM1.

Conclusions: Genes involved in the gastrointestinal hamartomatous polyposis, Hereditary Mixed Polyposis Syndrome and MUTYH-associated polyposis syndromes are not commonly altered in individuals with SPS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Bone Morphogenetic Protein Receptors, Type I / genetics*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • DNA Glycosylases / genetics*
  • Exons
  • Female
  • Gene Duplication
  • Germ-Line Mutation
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Introns
  • Male
  • Middle Aged
  • Neoplastic Syndromes, Hereditary / diagnosis
  • Neoplastic Syndromes, Hereditary / genetics*
  • PTEN Phosphohydrolase / genetics*
  • Sequence Deletion
  • Smad4 Protein / genetics*


  • GREM1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Smad4 Protein
  • BMPR1A protein, human
  • Bone Morphogenetic Protein Receptors, Type I
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • DNA Glycosylases
  • mutY adenine glycosylase