A SMAD4 mutation indicative of juvenile polyposis syndrome in a family previously diagnosed with Menetrier's disease

Background Menetrier's disease (MD) is a rare disease with unknown aetiology, characterized by hypertrophic folds within the fundus and body of the stomach. Aims 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. Conclusion 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.