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Massive juvenile polyposis of the stomach in a family with SMAD4 gene mutation

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Abstract

Relatively little is known on the genotype-phenotype correlations between SMAD4 gene mutations, juvenile polyposis of the intestine and Hereditary Hemorrhagic Teleangectasia. We describe a family in which the proband (a 46-year old woman) had massive polyposis of the stomach—leading to surgery—with high-grade dysplasia at histology. Molecular analysis was carried out using Next Generation sequencing techniques with Miseq Illumina Platforms and a minimal coverage of 40 reads. In the proband, the analysis showed the presence of a truncating mutation in the SMAD4 gene (c.1213dupC, a variant previously associated with juvenile polyposis and Hereditary Hemorrhagic Teleangectasia). The same mutation was detected in two other members of the family (father and brother of the proband), who showed massive polypoid involvement of the stomach at gastroscopy. By taking the family history, subtle evidence of Hereditary Teleangectasia was found (nasal bleeding and arterovenous malformations) in the three gene carriers. Colonoscopy showed polyp occurrence in all three affected members with SMAD4 mutation, with prevalence of adenomatous lesions in one (father), of hamartomas in the brother, and of a mix of histological types in the proband. The main features of the family can be summarized as follows: (A) In hereditary juvenile polyposis, lesions of different histology can be detected at colonoscopy; (B) In the gene carriers of SMAD4 mutations, lesions of the stomach require careful surveillance and, when necessary, surgical interventions; (C) Signs and symptoms of Hereditary Hemorrhagic Teleangectasia should be suspected (and searched) in individuals with SMAD4 constitutional mutations.

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Acknowledgement

We wish to thank Professor Carlo Sabbà - Department of Internal Medicine, University of Bari, Italy - for the many suggestions and helpful discussions regarding the management of Hereditary hemorragic teleangectasia.

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Authors and Affiliations

  1. Dipartimento di Medicina Diagnostica, Clinica e Sanità Pubblica, Università di Modena e Reggio Emilia, Policlinico, Via del Pozzo n.71, 41100, Modena, Italy

    Maurizio Ponz de Leon, Monica Pedroni, Federica Domati, Giuseppina Rossi & Luca Reggiani Bonetti

  2. Dipartimento di Ricerca Traslazionale e Oncologia Molecolare, Istituto Nazionale Tumori, Aviano, Pordenone, Italy

    Alessandra Viel

  3. Dipartimento Intregrato di Chirurgia, Nuovo Ospedale Civile Sant’Agostino ed Estense, Modena, Italy

    Claudio Luppi

  4. Endoscopia Digestiva, Nuovo Ospedale Civile Sant’Agostino ed Estense, Modena, Italy

    Rita Conigliaro

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  1. Maurizio Ponz de Leon
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  2. Monica Pedroni
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Correspondence to Maurizio Ponz de Leon.

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de Leon, M.P., Pedroni, M., Viel, A. et al. Massive juvenile polyposis of the stomach in a family with SMAD4 gene mutation. Familial Cancer 18, 165–172 (2019). https://doi.org/10.1007/s10689-018-0100-8

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