title: A SMAD4 mutation indicative of juvenile polyposis syndrome in a family previously diagnosed with Menetrier's disease.
abstract: BACKGROUND
  Menetrier's disease (MD) is a rare disease with unknown aetiology, characterized by hypertrophic folds within the fundus and body of the stomach.
  
  
  OBJECTIVE
  We investigated mutations of the candidate genes SMAD4, BMPR1A, TGF-α, and PDX1 within a family with MD.
  
  
  METHODS
  A large 4-generation family with MD was identified. This family had 5 cases of MD, 1 case of MD and juvenile polyposis syndrome (JPS) and 3 cases of JPS. Participants provided saliva for DNA extraction and completed a health questionnaire designed to assess conditions that may be found in patients with MD. Following pedigree analysis, we sequenced the coding regions of the SMAD4 and BMPR1A genes and the regulatory regions of the TGF-α and PDX1 genes in affected and non-affected family members.
  
  
  RESULTS
  No mutations were identified in the sequenced regions of BMPR1A, TGF-α, or PDX1. A dominant 1244_1247delACAG mutation of SMAD4 was identified in each of the subjects with JPS as well as in each of the subjects with MD. Although this mutation segregated with disease, there were also unaffected/undiagnosed carriers.
  
  
  CONCLUSIONS
  The 1244_1247delACAG mutation of SMAD4 is the cause of JPS and the likely cause of MD in a large family initially diagnosed with MD.
authors.affiliation: Department of Research, Gundersen Medical Foundation, LaCrosse, WI, United States.
authors.forename: James K
authors.initials: JK
authors.lastname: Burmester
authors.affiliation: Department of Internal Medicine and Graduate Medical Education, North Florida Regional Medical Center, Gainesville, FL, United States.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Bell
authors.affiliation: Office of Research Support, Christus Health, Irving, TX, United States.
authors.forename: Deanna
authors.initials: D
authors.lastname: Cross
authors.affiliation: University of Wisconsin Hospital and Clinics, Madison, WI, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Meyer
authors.affiliation: Department of Internal Medicine and Graduate Medical Education, North Florida Regional Medical Center, Gainesville, FL, United States. Electronic address: steven.yale@hcahealthcare.com.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Yale
mesh_terms: D000293:Adolescent; D000328:Adult; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics; D005260:Female; D005758:Gastritis, Hypertrophic / Q000150:complications / Q000235:genetics*; D018095:Germ-Line Mutation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D044483:Intestinal Polyposis / Q000151:congenital* / Q000235:genetics; D008297:Male; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010375:Pedigree; D051901:Smad4 Protein / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016211:Transforming Growth Factor alpha; C084010:pancreatic and duodenal homeobox 1 protein; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: Helicobacter pylori infection; Hypoproteinemic hypertrophic gastropathy; SMAD4 mutation; TGF-α signalling