Abstract
To describe the coexistence of mutations of both the multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and evaluate if it could be associated with more aggressive clinical manifestations of the two syndromes. Blood samples were obtained for genetic and biochemical analyses. The RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding regions, including the exon–intron boundaries, were amplified by PCR and directly sequenced. We identified two germline mutations in the proband: the first one, K666M, located at the exon 11 of RET proto-oncogene and the second one, IVS4+1G>T, located in the MEN1 gene. The functional characterization of IVS4+1G>T variation, located in the splicing donor site of exon 4 of MEN1 gene, caused the in-frame junction of exon 3 to exon 5, thus obtaining a shorter protein. The same proband’s germline mutations were found in 16 relatives out of 21 screened subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both the mutations. This is the second report in literature of coexistence in the same family of germline mutations of both RET proto-oncogene and MEN1 gene. The simultaneous presence of the two mutations was not apparently associated with more aggressive diseases, since at last follow-up all patients appeared to be disease-free or well compensated by medical therapy; finally, no one exhibited metastatic diseases.
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Acknowledgments
This work was supported by Umberto Di Mario Foundation, and “Banca d’Italia” grants. The authors would like to thank, for helpful suggestions, Dr. Giuseppe Di Stolfo from the Cardiology Unit, Dr. Stefano Santini and Dr. Palmina D’Arcangelo from the Clinical Chemistry Unit, Dr. Guido Valle and Dr. Antonio Maria Varraso from the Nuclear Medicine Unit of Scientific Institute “Casa Sollievo della Sofferenza”. We are grateful to G. Cafaro and A. Aucello for reception of patients and their families.
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The authors declare that they have no conflict of interest.
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Sandra Mastroianno and Massimo Torlontano have contributed equally to this study.
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Mastroianno, S., Torlontano, M., Scillitani, A. et al. Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian family. Endocrine 40, 481–485 (2011). https://doi.org/10.1007/s12020-011-9501-2
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DOI: https://doi.org/10.1007/s12020-011-9501-2