Role of GALNT12 in the genetic predisposition to attenuated adenomatous polyposis syndrome

PLoS One. 2017 Nov 2;12(11):e0187312. doi: 10.1371/journal.pone.0187312. eCollection 2017.

Abstract

The involvement of GALNT12 in colorectal carcinogenesis has been demonstrated but it is not clear to what extent it is implicated in familial CRC susceptibility. Partially inactivating variant, NM_024642.4:c.907G>A, p.(D303N), has been previously detected in familial CRC and proposed as the causative risk allele. Since phenotypes of the described carrier families showed not only CRC but also a polyp history, we hypothesized that GALNT12 could be involved in adenoma predisposition and consequently, in hereditary polyposis CRC syndromes. For that purpose, we have screened the GALNT12 gene in germline DNA from 183 unrelated attenuated polyposis patients. c.907G>A, p.(D303N) was detected in 4 cases (MAF = 1.1%) and no other candidate variants were found. After segregation studies, LOH analyses, glycosylation pattern tests and case-control studies, our results did not support the role of c.907G>A, p.(D303N) as a high-penetrance risk allele for polyposis CRC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Female
  • Gardner Syndrome / genetics*
  • Genetic Predisposition to Disease*
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • N-Acetylgalactosaminyltransferases / genetics*
  • Pedigree

Substances

  • GALNT12 protein, human
  • N-Acetylgalactosaminyltransferases

Supplementary concepts

  • Adenomatous Polyposis Coli, Attenuated

Grants and funding

The present study was supported by grants from the Instituto de Salud Carlos III, Spain (www.isciii.es) and European Regional Development FEDER funds: PI14/00929 to Pilar Garre, PI16/01292 to Trinidad Caldés and PI14/00230 to Clara Ruiz-Ponte. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.