title: A unifying working hypothesis for juvenile polyposis syndrome and Ménétrier's disease: specific localization or concomitant occurrence of a separate entity?
abstract: BACKGROUND
  Juvenile polyposis syndrome with gastric involvement may mimic Ménétrier's disease, which is correlated to transforming growth factor (TGF)α overproduction and PDX1 upregulation in the gastric fundus.
  
  
  OBJECTIVE
  We report a family with juvenile polyposis syndrome where one member showed typical features of Ménétrier's disease and concomitant Helicobacter pylori infection.
  
  
  METHODS
  We studied a 31-year-old woman belonging to a family with juvenile polyposis syndrome, who exhibited a particular form of hyperplastic gastropathy diagnosed as Ménétrier's disease with Helicobacter pylori infection.
  
  
  RESULTS
  TGFα overexpression and undetectable PDX1 expression were demonstrated in the fundic gastric biopsy specimens. In all affected members of the family we identified a 4-bp deletion in exon 9 of SMAD4 gene, a mutation usually associated with a more virulent form of juvenile polyposis syndrome with a higher incidence of gastric and colonic polyposis.
  
  
  CONCLUSIONS
  To explain the association of juvenile polyposis syndrome with Ménétrier's disease we hypothesized a new mechanism that involves TGFβ-SMAD4 pathway inactivation and TGFα overexpression related to Helicobacter pylori infection.
authors: Laboratory of Gastroenterology, Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy. a.piepoli@operapadrepio.it
authors: Ada
authors: A
authors: Piepoli
authors: Gianluigi
authors: G
authors: Mazzoccoli
authors: Anna
authors: A
authors: Panza
authors: Virginia
authors: V
authors: Tirino
authors: Giuseppe
authors: G
authors: Biscaglia
authors: Annamaria
authors: A
authors: Gentile
authors: Maria Rosa
authors: MR
authors: Valvano
authors: Celeste
authors: C
authors: Clemente
authors: Vincenzo
authors: V
authors: Desiderio
authors: Gianpaolo
authors: G
authors: Papaccio
authors: Michele
authors: M
authors: Bisceglia
authors: Angelo
authors: A
authors: Andriulli
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005758:Gastritis, Hypertrophic / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism; D016480:Helicobacter pylori; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D044483:Intestinal Polyposis / Q000150:complications / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009386:Neoplastic Syndromes, Hereditary / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D051901:Smad4 Protein / Q000235:genetics* / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation
chemical_list: D018398:Homeodomain Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; C084010:pancreatic and duodenal homeobox 1 protein