title: Germline variants in Hamartomatous Polyposis Syndrome-associated genes from patients with one or few hamartomatous polyps.
abstract: OBJECTIVE
  A subgroup of patients with hamartomatous polyps in the GI tract has a hereditary Hamartomatous Polyposis Syndrome with an increased risk of cancer. The distinction between patients with one or few polyps and patients with a syndrome can be difficult. A pathogenic germline mutation can be detected in a majority of HPS patients. This study investigates whether patients with one or few hamartomatous polyps could have a syndrome based on genetic screening of relevant genes.
  
  
  METHODS
  We designed a gene panel including 26 hamartomatous polyposis-associated genes. Using targeted Next Generation Sequencing, DNA samples from 77 patients with 84 hamartomatous polyps were sequenced. The detected germline variants were classified into pathogenicity classes.
  
  
  RESULTS
  We detected several germline variants, among them three in ENG, two in BMPR1A, one in PTEN, and one in SMAD4. Although some of the detected variants have been reported previously none could be definitely pathogenic or likely pathogenic.
  
  
  CONCLUSIONS
  Our study points towards that genetic testing for the Hamartomatous Polyposis Syndromes in patients with one or few polyps does not improve diagnostics, however we illustrate that the clinical significance of genetic variants can be difficult to interpret. A family history of polyps, cancer, or extraintestinal findings or a minimum of 3-5 polyps seems to be relevant information to include before genetic testing.
authors.affiliation: a Department of Clinical Genetics , Odense University Hospital , Odense C , Denmark ;|b Institute of Clinical Research, University of Southern Denmark , Odense C , Denmark ;
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Jelsig
authors.affiliation: a Department of Clinical Genetics , Odense University Hospital , Odense C , Denmark ;|b Institute of Clinical Research, University of Southern Denmark , Odense C , Denmark ;
authors.forename: Klaus
authors.initials: K
authors.lastname: Brusgaard
authors.affiliation: c Department of Pathology , Hvidovre University Hospital , Hvidovre , Denmark ;
authors.forename: Tine Plato
authors.initials: TP
authors.lastname: Hansen
authors.affiliation: d Department of Surgery , Odense University Hospital , Odense C , Denmark ;
authors.forename: Niels
authors.initials: N
authors.lastname: Qvist
authors.affiliation: a Department of Clinical Genetics , Odense University Hospital , Odense C , Denmark ;|b Institute of Clinical Research, University of Southern Denmark , Odense C , Denmark ;
authors.forename: Martin
authors.initials: M
authors.lastname: Larsen
authors.affiliation: e Department of Clinical Genetics , Vejle Hospital, Lillebaelt Hospital , Vejle , Denmark ;|f Institute of Regional Health Research, University of Southern Denmark , Odense C , Denmark ;
authors.forename: Anders
authors.initials: A
authors.lastname: Bojesen
authors.affiliation: g Department of Surgery , Hvidovre University Hospital , Hvidovre , Denmark.
authors.forename: Claus Buhl
authors.initials: CB
authors.lastname: Nielsen
authors.affiliation: a Department of Clinical Genetics , Odense University Hospital , Odense C , Denmark ;|b Institute of Clinical Research, University of Southern Denmark , Odense C , Denmark ;
authors.forename: Lilian Bomme
authors.initials: LB
authors.lastname: Ousager
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003110:Colonic Neoplasms / Q000175:diagnosis; D003718:Denmark; D000071063:Endoglin / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010580:Peutz-Jeghers Syndrome / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics*; D011127:Polyps / Q000473:pathology*; D012189:Retrospective Studies; D051901:Smad4 Protein / Q000235:genetics; D055815:Young Adult
chemical_list: C064206:ENG protein, human; D000071063:Endoglin; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Genetic variants; Juvenile polyposis syndrome; Peutz–Jeghers syndrome; high-throughput nucleotide sequencing; polyps